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BACKGROUND: Fluorosis is a common endemic disease, and its severity depends on the dose and duration of fluoride exposure. Bone morphogenetic protein 2 plays an important role in the pathogenesis of skeletal fluorosis. OBJECTIVE: To explore the relationship between the expression of bone morphogenetic protein 2 and bone fluoride content in rabbit femur and the changes of bone formation markers, osteocalcin and procollagen l N-terminal propeptide, under different fluoride concentrations. METHODS: Sixteen New Zealand white rabbits were randomly divided into control group, low dose group, middle dose group, and high dose group, with four rabbits in each group. Animals drank tap water containing 0, 100, 200, and 400 mg/L sodium fluoride, respectively. The experimental period was 6 months. During the feeding period, all animals had free access to water and food. Occurrence and development of dental fluorosis was observed regularly. The fluorine content in rabbit femur was determined by ashing distillation-fluorine reagent colorimetry. The expression of bone morphogenetic protein 2 in femur was detected by western blot. The levels of osteocalcin and procollagen l N-terminal propeptide in serum were detected by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: The rabbits in fluoride exposure groups showed different degrees of fluorosis. In the low dose group, mild fluorosis was found and mainly manifested with tarnished teeth and some fine lines. The middle dose group was dominated by moderate dental fluorosis, manifested as uneven tooth surface and color. Some models with dental defects presented with severe dental fluorosis. The high dose group was dominated by severe dental fluorosis, which was characterized by dull tooth surface and deformed tooth development. The bone fluoride content in the femur of rabbits increased with the increase of fluoride intake, which was higher in the high dose group than the other three groups (P < 0.01, P < 0.001). The serum osteocalcin level in the high dose was higher than that in the control group (P < 0.05) and the serum level of procollagen l N-terminal propeptide was lower than that in the control group and the low dose group (P < 0.05). The expression of bone morphogenetic protein 2 in the femur was higher in the low dose group than the control and high dose groups (P < 0.05). Pearson correlation analysis showed that the expression of bone morphogenetic protein 2 in the low dose group was positively correlated with the bone fluoride content (r=0.951, P < 0.05), while there was no significant correlation between the expression of bone morphogenetic protein 2 and the content of bone fluoride in the middle and high dose groups (r=0.889, r=-0.116, P > 0.05). To conclude, the expression of bone morphogenetic protein 2 in rabbit femur is bidirectionally related to bone fluoride concent, which is related to fluoride exposure concentration, that is, too high or too low fluoride content will alter the expression of bone morphogenetic protein 2. [ABSTRACT FROM AUTHOR]

Nanohydroxyapatite (nanoHA) is the major mineral component of bone. It is highly biocompatible, osteoconductive, and forms strong bonds with native bone, making it an excellent material for bone regeneration. However, enhanced mechanical properties and biological activity for nanoHA can be achieved through enrichment with strontium ions. Here, nanoHA and nanoHA with a substitution degree of 50 and 100% of calcium with strontium ions (Sr-nanoHA_50 and Sr-nanoHA_100, respectively) were produced via wet chemical precipitation using calcium, strontium, and phosphorous salts as starting materials. The materials were evaluated for their cytotoxicity and osteogenic potential in direct contact with MC3T3-E1 pre-osteoblastic cells. All three nanoHA-based materials were cytocompatible, featured needle-shaped nanocrystals, and had enhanced osteogenic activity in vitro. The Sr-nanoHA_100 indicated a significant increase in the alkaline phosphatase activity at day 14 compared to the control. All three compositions revealed significantly higher calcium and collagen production up to 21 days in culture compared to the control. Gene expression analysis exhibited, for all three nanoHA compositions, a significant upregulation of osteonectin and osteocalcin on day 14 and of osteopontin on day 7 compared to the control. The highest osteocalcin levels were found for both Sr-substituted compounds on day 14. These results demonstrate the great osteoinductive potential of the produced compounds, which can be exploited to treat bone disease. [ABSTRACT FROM AUTHOR]

Calcium phosphate (CaP) coating-modified titanium (Ti) surfaces have been developed to improve the biological activity and osseointegration of Ti-based implants. However, these coatings always lack three-dimensional micro/nanostructures mimicking bone tissue. To fabricate hierarchical CaP coating structures and enhance the bioactivity of Ti implants, this study developed a novel hydrothermal method for preparing biomimetic three-dimensional CaP network structures on alkali-treated Ti surface with the assistance of oleic acid. Moreover, the growth mechanism of the CaP network structure was investigated, and its biocompatibility was evaluated by co-culture with preosteoblasts. The coatings were mainly composed of HA nanowires, which grew vertically along the titanate nanowires and further self-assembled into macropores. Compared to the pristine Ti surface, this hierarchical network structure showed superior hydrophilicity, elevated roughness, and improved cell attachment, proliferation, and osteogenic differentiation. Furthermore, this CaP structure demonstrated significantly higher alkaline phosphatase (ALP) activity and upregulated the expression of osteopontin (OPN) and osteocalcin (OCN) in comparison with similar titanate structures, suggesting improved bioactivity of the hierarchical CaP network structure. These improvements were probably attributed to hierarchical micro/nanostructure and CaP chemistry. The above findings indicate that this method effectively fabricates hierarchical CaP network structures on Ti-based substrates, which construct a favorable microenvironment for inducing osteogenic differentiation. [ABSTRACT FROM AUTHOR]

We evaluated the effects of obesity and osteocalcin on glucose metabolism in the brain. A total of 179 healthy men were enrolled in this study. After preprocessing positron emission tomography images, including by performing coregistration, spatial normalization, and smoothing, regression analysis was conducted to identify the correlation between body mass index, osteocalcin, and brain glucose metabolism. Body mass index was positively correlated with brain glucose metabolism in the anterior lobe of the right cerebellum, the anterior and posterior lobes of the left cerebellum, the right middle frontal gyrus (Brodmann area 9), the right cingulate gyrus (Brodmann area 32), the right anterior cingulate (Brodmann area 32), the left middle frontal gyrus (Brodmann area 10), and the subgyral area of the left frontal lobe. Osteocalcin was negatively correlated with glucose metabolism in the anterior lobe of the left cerebellum. Body mass index was positively correlated with brain glucose metabolism in the prefrontal cortex and cerebellum. Osteocalcin levels were negatively correlated with brain glucose metabolism in the left cerebellum. [ABSTRACT FROM AUTHOR]

Background: Coagulation factors, anticoagulants, and fibrinolytic proteins are important for hemostasis, and mutations affecting these proteins causes some rare inherited bleeding disorders that are particularly challenging to diagnose. Aims: This review provides current information on rare inherited bleeding disorders that are difficult to diagnose. Material & Methods: A review of the literature was conducted for up to date information on rare and difficult to diagnose bleeding disorders. Results: Some rare bleeding disorders cause an inherited deficiency of multiple coagulation factors (F), such as combined FV and FVIII deficiency and familial vitamin K‐dependent clotting factor deficiency. Additionally, congenital disorders of glycosylation can affect a variety of procoagulant and anticoagulant proteins and also platelets. Some bleeding disorders reflect mutations with unique impairments in the procoagulant/anticoagulant balance, including those caused by F5 mutations that secondarily increase the plasma levels of tissue factor pathway inhibitor as well as THBD mutations that increase functional thrombomodulin in plasma or cause a consumptive coagulopathy due to thrombomodulin deficiency. Some bleeding disorders accelerate fibrinolysis due to loss‐of‐function mutations in SERPINE1 and SERPINF2 or in the case of Quebec platelet disorder, a duplication mutation that rewires PLAU and selectively increases expression in megakaryocytes, resulting in a unique platelet‐dependent gain‐of‐function defect in fibrinolysis. Discussion: Current information on rare and difficult to diagnose bleeding disorders indicates they have unique clinical and laboratory features, and pathogenic characteristics to consider for diagnostic evaluation. Conclusion: Laboratories and clinicians should consider rare inherited disorders, and difficult to diagnose conditions, in their strategy for diagnosing bleeding disorders. [ABSTRACT FROM AUTHOR]

Introduction: The study evaluates the levels of matrix metalloprotease‐8 (MMP‐8), and Cathepsin‐K (CatK) in peri‐implant crevicular fluid (PICF) among patients with immediate loaded (IL) and delayed‐loaded (DL) implants at different time points to know the inflammation and osteogenic status. Methods: The study population consisted of two groups (n = 25, each group) with a mean age of 28.7 ± 3.5 years, and PICF was collected. MMP‐8 and CatK levels were quantified through ELISA. Results: We observed the concentrations of inflammatory markers (MMP‐8 and CatK) at three time points in the IL and DL groups. The mean concentration of MMP‐8 in the IL group was 9468 ± 1230 pg/mL, 5547 ± 1088 pg/mL, and 7248 ± 1396 pg/mL at 2 weeks, 3 months, and 12 months, respectively; while in the DL group was 10 816 ± 779.7 pg/mL, 9531 ± 1245 pg/mL, and 9132 ± 1265 pg/mL at 2 weeks, 3 and 12 months, respectively. The mean concentration of Cat‐K in the IL group was observed at 422.1 ± 36.46 pg/mL, 242.9 ± 25.87 pg/mL, and 469 ± 75.38 pg/mL at 2 weeks, 3, and 12 months, whereas in the DL group was 654.6 ± 152.9 pg/mL, 314.7 ± 28.29 pg/mL, and 539.8 ± 115.1 pg/mL at 2 weeks, 3 months and 12 months, respectively. Conclusion: In this study, the levels of CatK and MMP‐8 levels decline at 12 months in both groups, and the IL group shows lower values compared to the DL group; however, no significant changes were observed after analyses were adjusted for multiple comparisons (p > 0.025). Therefore, there is not much difference observed in the inflammation process between immediate and delayed loading. (Clinical trial identifier: CTRI/2017/09/009668). [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD), the non-psychoactive component of the Cannabis sativa plant, is marketed as a potential therapeutic agent and has been studied for its roles in reducing inflammation and managing neuropathic pain. Some studies have reported that CB1 and CB2 receptor activation can attenuate and reverse bone loss in experimental animal models. Despite this, little is known about the impact of CBD on fracture healing. We investigated the effects of CBD in vitro using human osteoprogenitor cells and in vivo via murine femur fracture and osteoporosis models. In vitro mesenchymal stem cells were treated with increasing concentrations of crystalized pharmaceutical grade CBD or vehicle solution. Cell viability and proliferation were significantly increased in cells treated with CBD compared to vehicle control. Osteocalcin expression was also significantly higher in the CBD-treated human stem cells compared to vehicle control. In vivo the effect of CBD on bone mineral density and fracture healing in mice was examined using a two-phase experimental approach. Fluoxetine was used for pharmacologic induction of osteoporosis and surgical oophorectomy (OVX) was used for hormonal induction of osteoporosis. X-ray and microCT analysis showed that CBD prevented both fluoxetine- and OVX-induced osteoporosis. We found that while OVX resulted in delayed bone healing in control mice, CBD-pretreated mice exhibited normal bone healing. Collectively these in vitro and in vivo findings suggest that CBD exerts cell-specific effects which can be exploited to enhance bone metabolism. These findings also indicate that CBD usage in an osteoporotic population may positively impact bone morphology, warranting further research. [ABSTRACT FROM AUTHOR]

Background: The differential responses of the myokine irisin, in combination with changes in markers and regulators of bone remodeling to high-intensity interval exercise of high and low impact, were examined in 18 young adult females (22.5 ± 2.7 years). Methods: Participants performed two high-intensity interval exercise trials in random order: running on a treadmill and cycling on a cycle ergometer. Trials consisted of eight 1 min running or cycling intervals at ≥ 90% of maximal heart rate, separated by 1 min passive recovery intervals. Blood samples were collected at rest (pre-exercise) and 5 min, 1 h, and 24 h following each exercise trial. Irisin, osteocalcin, sclerostin, osteoprotegerin (OPG), receptor activator nuclear factor kappa-β ligand (RANKL), and parathyroid hormone (PTH) were analyzed in serum, with post-exercise concentrations being corrected for exercise-induced changes in plasma volume. Results: Irisin was elevated 24 h post-exercise compared to its resting values in both trials (20%, p < 0.05) and was higher after cycling compared to running (exercise mode effect, p < 0.05) with no interaction. Osteocalcin, sclerostin, PTH, and RANKL increased from pre- to 5 min post-exercise (18%, 37%, 83%, and 33%, respectively, p < 0.05), returning to baseline levels in 1 h, with no trial or interaction effects. OPG showed a time effect (p < 0.05), reflecting an overall increase at 5 min and 1 h post-exercise, which was not significant after the Bonferroni adjustment. Conclusions: In young adult females, high-intensity interval exercise induced an immediate response in markers and regulators of bone remodeling and a later response in irisin concentrations, which was independent of the gravitational impact. [ABSTRACT FROM AUTHOR]

Bioarchaeologists can further investigate human bone metabolism at the biomolecular level by incorporating biochemical methods into their research. Recently, there has been a focus on osteocalcin, an abundant non-collagenous bone protein, because of its clinically identified relationship with biological factors (i.e., age and sex), activity, and pathological conditions (i.e., disease). For this study, osteocalcin was extracted and quantified from the femora of 27 individuals from the Fortress of Louisbourg (1713-1758) skeletal collection to explore if the clinical relationship between osteocalcin and sex, age, activity, and pathological conditions can also be established in archaeological bone. However, no significant relationships between osteocalcin concentrations and biological factors (i.e., age and sex), activity, or pathological conditions were identified. This is the first study to quantify osteocalcin from archaeological human skeletal remains from a Canadian context and provides another example of how this method may be used to study stress in bioarchaeological populations. [ABSTRACT FROM AUTHOR]

An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose metabolism. Here, we describe the high‐resolution X‐ray crystal structure of decarboxylated osteocalcin under acidic conditions. Decarboxylated osteocalcin at pH 2.0 retains the α‐helix structure of native osteocalcin with three γ‐carboxyglutamic acid residues at neutral pH. This implies that decarboxylated osteocalcin is stable under an acidic environment in bone. In addition, site‐directed mutagenesis revealed that Glu17 and Glu21 are important for the adiponectin‐inducing activity of decarboxylated osteocalcin. These findings suggest that the receptor of decarboxylated osteocalcin responds to the negative charge in helix 1 of osteocalcin. [ABSTRACT FROM AUTHOR]

Background: Osteocalcin (OC), also known as bone Gla (gamma-carboxyglutamic acid) protein, is a marker of bone formation. OC has effect on glucose and fat metabolism. Role of OC in type 2 diabetes mellitus (T2DM) is not well studied in Indian population. Our study aimed to see the relationship between OC and parameters of glucose metabolism in type 2 diabetes mellitus. Methods: This cross-sectional study included 120 subjects with T2DM. In each subject, fasting insulin, serum osteocalcin (measured by ELISA), fasting plasma glucose (FPG), post prandial plasma glucose (PPG), and glycated Hb (HbA1c) were measured. HOMA 2.0 model was used to measure insulin resistance (HOMA-IR) and β-cell function (HOMA-β). Then, serum osteocalcin levels were correlated with HOMA-IR, HOMA-β, FPG, PPG, and HbA1c. Results: Serum OC levels reduced with increase in insulin resistance (HOMA-IR) (r = −0.274, p = 0.004); however, there was no association with the beta cell function. OC had negative association with FPG (r = −0.14, p = 0.12) and PPG (r = −0.123, p = 0.18); however, it was statistically insignificant. Glycated hemoglobin (HbA1c) was significantly reduced in diabetic patients with higher OC levels (r = −0.208, p = 0.025). Conclusion: Serum OC has significant association with insulin resistance and HbA1c in subjects with T2DM, which might suggest possible role of serum OC in glucose metabolism in T2DM. [ABSTRACT FROM AUTHOR]

Osteoporosis has become a serious public health problem especially in postmenopausal women. This work aims to assess both the function and mechanism of SDH5 in osteoporosis. The animal model of osteoporosis in Sprague-Dawley rats was established by utilizing ovariectomy (OVX). The trabecular bone morphometry had been determined by micro-CT, and tibia injury of rats was detected through HE and alcian blue staining. Meanwhile, the levels of oxidative stress factors, including malondialdehyde, catalase, glutathione peroxidase (GSH-Px), and superoxide (SOD), were detected by ELISA. The proliferation and apoptosis of osteoblasts isolated from OVX-induced rats were found out by CCK-8 and flow cytometry, respectively. The expression of SDH5, Osterix, Type I collagen (CoL1A1), osteocalcin (OC), SOD1, SOD2, p-MyD88/MyD88, and p-NF-κB p65/NF-κB p65 was assessed by Western blot. The effect and mechanism of SDH5 knockdown on osteoporosis were verified by lipopolysaccharide treatment. In the osteoporosis rat model, the expression of SDH5 had an up-regulated tend. A higher bone mineral density value was found in the SDH5 knockdown group. SDH5 inhibition ameliorated bone loss, mitigated bone histopathological injury, alleviated oxidative stress, and elevated osteogenic marker protein expression in vivo and in vitro. SDH5 down-regulation also promoted the proliferation and restrained apoptosis of osteoblasts extracted from OVX-induced rats. Furthermore, we found that the underlying mechanism was associated with the inhibition of the MyD88/NF-κB pathway. Down-regulation of SDH5 mitigates the damage of osteoporosis both in vivo and in vitro via inhibiting the MyD88/NF-κB signaling activation. [ABSTRACT FROM AUTHOR]

Background: Using bone turnover marker (BTM) monitoring to identify "quick losers" who may develop osteoporosis in the coming years is one of the main challenges in clinical practice. This study was implemented to examine the association of BTMs with bone mineral density (BMD) as well as to determine their relationship with the fracture risk assessment tool (FRAX) in women in the postmenopausal period. Materials and Methods: This study was observational cross-sectional research that was done on women between the ages of 50 and 65 who were in the postmenopausal period. A dual-energy X-ray absorptiometry was applied to select 120 eligible women with normal BMD and 120 women without normal BMD. BTMs were assessed using enzyme-linked immunosorbent assay. Osteoporosis's Odds Ratio (OR) was estimated using a confounder-adjusted logistic regression model. The area under curve was calculated for the differentiation of low BMD in the postmenopausal period through receiver-operator characteristic (ROC) curves. To assess the probability of major osteoporotic fracture and hip fracture for the future 10 years, FRAX was applied. Results: Higher serum osteocalcin (OC) (OR: 1.134, 95% confidence interval [CI]: 1.086-1.184), osteopontin (OP) (OR: 1.180; 95%CI: 1.105-1.261), and alkaline phosphatase (ALP) (OR: 1.007; 95%CI: 1.001-1.144) concentrations were potential risk factors for developing low BMD in women after menopause. The area under curve (AUC) (95%CI) for OC, OP, and ALP was 0.75 (0.668-0.8130), 0.75 (0.685-0.812), and 0.602 (0.524-0.670), respectively. ROC analysis indicated that at the cut-off point of 16.28 ng/mL, sensitivity and specificity were 70.3% and 70.9%, respectively, for OC. Furthermore, at the cut-off point of 28.85 ng/mL, the sensitivity of 70.3% and specificity of 66.6% were obtained for OP. The serum OC and OP were significantly related to hip and major osteoporotic fractures (P < 0.05). Conclusion: The higher serum concentration of OC, OP, and ALP had significant associations with lower BMD. These BTMs can be complementary tools and helpful in the postmenopausal period as measures for screening of bone loss and possible bone fracture. [ABSTRACT FROM AUTHOR]

Iron plays important roles in bone health as it is required as a cofactor for renal 25-hydroxyvitamin D-1α-hydroxylase, which is involved in the production of 1,25-dihydroxyvitamin D3 (active vitamin D), and regulates the expression of proteins involved bone formation. Herein, we investigated the eff ects of dietary iron supplementation on bone formation in iron-defi cient rats. Male Wistar rats were fed a control (n = 12) or iron-defi cient diet (n = 18) for 30 days, after which 6 rats in the iron-defi cient group were switched to the control diet for 14 days. At the end of the 30-day period, hemoglobin, liver iron, serum 1,25-dihydroxyvitamin D3, and serum osteocalcin concentrations, and femoral bone mineral density (BMD) were found to be signifi cantly lower in iron-defi cient rats than that in control rats. Following dietary iron supplementation, hemoglobin and liver iron concentrations elevated signifi cantly in irondefi cient rats; however, they were not restored to the normal levels. Additionally, dietary iron supplementation increased serum 1,25-dihydroxyvitamin D3 and osteocalcin concentrations and femoral mRNA expression of Bglap and Col1a1 in iron-defi cient rats, which were downregulated by iron defi ciency, to levels similar to that in control rats. However, femoral BMD was not recovered with dietary iron supplementation. These results suggest that iron defi ciency-induced downregulation of bone formation can potentially be reversed by dietary iron supplementation. Furthermore, elevated serum 1,25-dihydroxyvitamin D3 concentrations due to dietary iron supplementation could be responsible for increased expression of bone formation markers in iron-defi cient rats. [ABSTRACT FROM AUTHOR]

Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide); and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). BTMs are usually measured by enzyme-linked immunosorbent assay or automated immunoassay. Sources contributing to BTM variability include uncontrollable factors (eg, age, gender, ethnicity) and controllable factors, particularly relating to collection conditions (eg, fasting/feeding state, and timing relative to circadian rhythms, menstrual cycling, and exercise). Pregnancy, season, drugs, and recent fracture(s) can also affect BTMs. BTMs correlate with other methods of assessing bone turnover, such as bone biopsies and radiotracer kinetics, and can usefully contribute to diagnosis and management of several diseases such as osteoporosis, osteomalacia, Paget's disease, fibrous dysplasia, hypophosphatasia, primary hyperparathyroidism, and chronic kidney disease–mineral bone disorder. [ABSTRACT FROM AUTHOR]

The study aims to evaluate a standardized Sprague-Dawley (SD) rat model for postmenopausal osteoporosis (PMO) research, including the selection of animals, surgical procedures, anesthetic dosage, and supportive care for a speedy recovery, osteoporotic induction, and biochemical and DEXA scan evaluation. Midventral ovariectomy was performed by removing ovaries to simulate a postmenopausal clinical condition in SD rats. The serum markers, estradiol, osteocalcin, and tartrateresistant acid phosphatase levels in serum were estimated, and PMO status was confirmed with a DEXA scan by evaluating the whole bone mineral density and bone mineral content. The ovariectomized rat (OVX) showed a sharp loss in bone mass and mineral content and serum calcium significantly lowered from 11.21±0.85 mg/dl to 6.34±0.69 mg/dl, magnesium from 2.87±0.43 mg/dl to 2.11±0.31 mg/dl and phosphorus 4.03±0.58 mg/dl to 2.73±0.87 mg/dl respectively. The OVX rats showed a significant reduction in osteocalcin and estradiol values of 1.08±0.68 ng/ml and 67.28±11.46 pg/ml at the end of 6 months, respectively. In OVX animals, the total bone mineral density obtained by DEXA scan was 0.164 ±0.004 g/cm2 compared to sham control (0.183 ±0.006 g/cm2). Midventral ovariectomy can be considered an accepted surgical procedure to create an animal model for understanding PMO-associated bone loss. Serum estradiol evaluation along with osteocalcin, calcium, and DEXA scan standardized the status of PMO for detailed study. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Advanced Platelet‐Rich Fibrin (A‐PRF+), Leukocyte Platelet‐Rich Fibrin (L‐PRF), and injectable Platelet‐Rich Fibrin (i‐PRF) on osteogenesis of a human osteoblast‐like cell line in vitro. Background: Different PRF protocols are used in clinical dentistry in the last years. Recent literature documented the positive impact of PRF derivatives in vivo and in vitro, on different types of cells. However, hardly any literature comparing the new protocols for PRF (the A‐PRF+ and i‐PRF) with the original protocol of PRF (L‐PRF) is present for osteoblast‐like cells. Materials and Methods: A‐PRF+, L‐PRF, and i‐PRF were prepared from six male donors and pre‐cultured with 10 mL culture medium for 6 days. 5 x 103 cells/ml osteoblasts from the osteoblast cell line (U2OS) were seeded and cultured either with conditioned medium derived from the different PRF conditions or with regular culture medium. At five different time points (0, 7, 14, 21, 28 days), the osteogenic capacity of the cells was assessed with Alizarin Red S to visualize mineralization. Also in these cells, the calcium concentration and alkaline phosphatase activity were investigated. Using qPCR, the expression of alkaline phosphatase, osteocalcin, osteonectin, ICAM‐1, RUNX‐2, and collagen 1a was assessed. Results: In osteoblast‐like cells cultured with conditioned medium, the A‐PRF+ conditioned medium induced more mineralization and calcium production after 28 days of culturing compared with the control (p <.05). No significant differences were found in the extent of cell proliferation between the different conditions. RUNX‐2 and osteonectin mRNA expression in the cells were lower in all PRF‐stimulated cultures compared with control at different time points. The i‐PRF‐conditioned medium induced more ALP activity (p <.05) compared with control and osteoblasts‐like cells differentiated more compared with osteoblasts cultured with L‐PRF. Conclusions: The three PRF preparations seem to have the capacity to increase the osteogenic potential of osteoblast‐like cells. A‐PRF+ seems to have the highest potential for mineralization, while i‐PRF seems to have the potential to enhance early cell differentiation. [ABSTRACT FROM AUTHOR]

Accumulating evidence has documented that microRNAs (miRNAs or miRs) function as important post‑transcriptional regulators of the differentiation of mesenchymal stem cells (MSCs), including human adipose‑derived mesenchymal stem cells (hADSCs); however, their roles in hADSC osteogenic differentiation require further investigation. The present study aimed to investigate the role of miRNAs in the osteogenic differentiation of hADSCs and to elucidate the underlying molecular mechanisms. Using an miRNA microarray, it was found that 24 miRNAs were upregulated and 14 miRNAs were downregulated compared with the undifferentiated cells, and miR‑29b‑3p (miR‑29b) was selected for further experiments. Functional experiments revealed that the upregulation of miR‑29b by agomir‑29b significantly enhanced alkaline phosphatase (ALP) activity and the mineralization of extracellular matrix (ECM), and led to an increase in the mRNA and protein levels of osteogenic marker genes, including runt‑related transcription factor 2 (Runx2), osteopontin (OPN), osteocalcin (OCN) and bone sialoprotein (BSP), whereas the knockdown of miR‑29b suppressed these processes. In addition, phosphatase and tensin homolog (PTEN), a negative regulator of the AKT/β‑catenin pathway, was identified as a direct target of miR‑29b in the hADSCs. Moreover, it was observed that the overexpression of miR‑29b activated the AKT/β‑catenin signaling pathway by inhibiting PTEN expression in the hADSCs. Most importantly, it was also found that the overexpression of PTEN reversed the promoting effects of miR‑29b on osteogenic differentiation. On the whole, these findings suggest that miR‑29b promotes the osteogenic differentiation of hADSCs by modulating the PTEN/AKT/β‑catenin signaling pathway. Thus, this miRNA may be a promising target for the active modulation of hADSC‑derived osteogenesis.

ObjectiveWe tested whether bone-related extracellular vesicle phenotypes changed after initiating antiretroviral therapy (ART) and determined whether changes in levels of extracellular vesicles correlated with changes in bone mineral density (BMD).DesignExtracellular vesicle phenotypes were measured in blinded serum samples from 15 adults with HIV at baseline, 1, 3, 6 and 12 months after ART initiation. Not all samples were available at each time point so we averaged early (TP1, 1-3 months) and late (TP2, 6-12 months) time points.MethodsExtracellular vesicles were stained for osteocalcin (OC), RANKL (CD254), RANK (CD265), M-CSF (macrophage colony stimulating factor), and CD34. Serum OC, procollagen type I N-terminal propeptide (P1NP), and C-terminal telopeptide of type 1 collagen (CTx) were also measured.ResultsBMD significantly decreased from baseline to 12 months. Levels of OC+EVs, serum OC, serum P1NP, and CTx were significantly higher at early and late time points compared with baseline. Increases in EVs expressing OC, RANKL, RANK, and CD34 from baseline to TP1 were associated with decreases in total hip BMD from baseline to 12 months. Change in serum OC, P1NP, and CTx from baseline to TP1 or TP2 did not correlate with change in BMD.ConclusionEarly changes in extracellular vesicles expressing markers of bone activity were associated with total hip bone loss 12 months after ART initiation. These data suggest that serum extracellular vesicles may serve as novel biomarkers of bone remodeling. Future studies are required to determine if extracellular vesicles contribute to the effects of ART on changes in bone turnover markers and BMD.

Abstract Background Calcific aortic valve disease (CAVD) is the second leading cause of adult heart diseases. The purpose of this study is to investigate whether miR-101-3p plays a role in the human aortic valve interstitial cells (HAVICs) calcification and the underlying mechanisms. Methods Small RNA deep sequencing and qPCR analysis were used to determine changes in microRNA expression in calcified human aortic valves. Results The data showed that miR-101-3p levels were increased in the calcified human aortic valves. Using cultured primary HAVICs, we demonstrated that the miR-101-3p mimic promoted calcification and upregulated the osteogenesis pathway, while anti-miR-101-3p inhibited osteogenic differentiation and prevented calcification in HAVICs treated with the osteogenic conditioned medium. Mechanistically, miR-101-3p directly targeted cadherin-11 (CDH11) and Sry-related high-mobility-group box 9 (SOX9), key factors in the regulation of chondrogenesis and osteogenesis. Both CDH11 and SOX9 expressions were downregulated in the calcified human HAVICs. Inhibition of miR-101-3p restored expression of CDH11, SOX9 and ASPN and prevented osteogenesis in HAVICs under the calcific condition. Conclusion miR-101-3p plays an important role in HAVIC calcification through regulation of CDH11/SOX9 expression. The finding is important as it reveals that miR-1013p may be a potential therapeutic target for calcific aortic valve disease.

Objectives: Osteocalcin, a protein from osteoblasts, affects bone mineralization and turnover. This study evaluates the association between fasting serum osteocalcin and bone mineral density (BMD) in renal transplant recipients. Materials and Methods: This study recruited 66 renal transplant recipients. We analyzed blood biochemistry studies from fasting blood samples. The serum osteocalcin levels were measured using a commercial enzyme immunoassay kit. We measure BMD by dual-energy X-ray absorptiometry in lumbar vertebrae (L2–L4). By the World Health Organization classification, we group recipients into three groups: normal, osteopenia, and osteoporosis. Results: Of the renal transplant recipients, 8 patients (12.1%) were osteoporosis, and 28 patients (42.4%) were osteopenia. From normal to osteoporosis groups, the osteoporosis group has highest serum osteocalcin (P < 0.001), alkaline phosphatase (P = 0.005), lowest body mass index (P = 0.015), and body weight (P = 0.008). Females had lower lumbar BMD than males among recruited renal transplant recipients (P = 0.023). In the multivariate forward stepwise linear regression analysis, body weight (adjusted R2 change = 0.138; P = 0.010), and logarithmically transformed osteocalcin (log-osteocalcin; adjusted R2 change = 0.131; P = 0.012) can predict lumbar BMD in the renal transplant recipients. Conclusion: Our study showed that fasting serum osteocalcin concentration was negatively correlated with the lumbar BMD in renal transplant recipients.

I previously reported that F-box/leucine-rich repeat protein 14 (FBXL14) expressed in periosteum-derived cells, and F-box and WD-40 domain-containing protein 2 (FBXW2) in the periosteum form a fiber-like structure. Here, two culture medium conditions, that is, media with and without ascorbic acid, were compared during explant culture. In the absence of ascorbic acid, the expression patterns of osteocalcin, FBXW2, and elastin were compared using fluorescent immunostaining during weeks 3–5. By observing the periosteum, cambium layer and bone, I demonstrated FBXL14 expression in micro-vessels and bone lacuna. Fluorescent immunostaining revealed that, without ascorbic acid, the FBXL14 layer was thin. Conversely, in the presence of ascorbic acid, FBXL14 formed a thick membrane-like structure inside the periosteum, and the multilayer of periosteum-derived cells (PDCs) was strong. The expression patterns of osteocalcin and FBXW2 were similar. Elastin retained its fiber structure for up to five weeks. Although osteocalcin and FBXW2 were expressed in regions similar to elastin, they could not retain their fiber structures. In conclusion, FBXL14 appears to play a role in preparing a native scaffold for forming a multilayered sheet of PDCs inside the periosteum. FBXW2 and osteocalcin appear to separate from elastic fibers during calcification.

The study was planned to explore the influence of one type of hydrophilic statins (rosuvastatin) on the level of serum osteocalcin, N-telopeptide of type 1 collagen (NTx), calcium, and phosphorus. In addition to calcium, phosphorus, and magnesium in femur bone ash of female ovariectomized rats. Thirty female rats aged 2.5-3 months were divided as follows, sham group, ovariectomized (ovx) group as a model of osteoporosis, and (ovx) group treated with 20mg /kg of rosuvastatin for 60 days. Blood samples were collected after 30 and 60 days of the experiment for biochemical analysis. Besides, after 60 days of the treatment, right femur bones were excised and ashed to estimate calcium, phosphorus, and magnesium. The results showed a significant elevation in serum osteocalcin, (NTx), calcium, and phosphorus, in addition to elevation in osteoclasts number and deceased osteoblasts and thickness of trabecular bone in the (ovx) group compared to the sham, while treatment with rosuvastatin caused a significant reduction in osteocalcin, (NTx), calcium and phosphorus after 60 days. Also, the results revealed a significant reduction in the percentage of (Ca, P and Mg) content in bone ash of the (ovx) group compared to the sham group. However, rosuvastatin treatment led to a significant elevation in the percentage of calcium and inorganic phosphate in bone ash and increased the thickness of trabecular bone and development in osteocytes compared with ovariectomized rats. The conclusion of the present study, rosuvastatin has a positive effect on the bone of ovariectomized rats.

Background: Glucocorticoids are widely used in the clinical setting. The direct impacts of glucocorticoids on bones involve both transient and early rise in bone resorption and long-term inhibition of bone formation. Leptin enhances the differentiation of human bone marrow stromal cells into osteoblasts, suppresses the generation of osteoclasts and attenuates the reduction in bone formation. Objectives: This study aimed to assess the effects of prednisolone on causing osteoporosis in rats and the effects of leptin on osteoporotic rats. Material and Methods: The study was performed on 21 adult male white albino rats. They were divided equally into; control, osteoporotic and treated groups. The osteoporotic and treated groups were given 5 mg/kg/day oral prednisolone for 3 months. The treated group was given10 μg/kg/day intraperitoneal (IP) leptin for the next 2 months. Blood samples were collected for determination of serum calcium, phosphorous, alkaline phosphatase and osteocalcin levels. Bone of the right femur was used for histopathological examination. Results: The osteoporotic group had a highly significant decrease in serum calcium and phosphorus, in addition to significant increase serum alkaline phosphatase and osteocalcin. Also, there was decrease in cortical bone thickness and number of osteocyte-containing lacunae and increased number of osteocyte-free lacunae in osteoporotic group. Treatment with leptin improved both biochemical and structural changes in prednisolone induced osteoporosis. Conclusions: Leptin antagonizes the effects of glucocorticiods induced osteoporosis. It normalizes serum calcium and phosphorus. It improves bone mineral density and bone size.

The mechanism of osteoporosis (OP) development in systemic sclerosis (SSc) remains unclear.Objective: to assess bone mineral density (BMD) and the level of bone metabolism markers (osteocalcin — OC, — C-terminal type I collagen telopeptides — b-CrossLaps) in the blood serum of patients with SSc.Patients and methods. 65 patients with SSc were examined, 6 (9%) men and 59 (91%) women, the average age was 51 [39; 61] year (main group), and 35 healthy individuals comparable in anthropometric parameters (control group). In all individuals were assessed the most important populational risk factors for OP. BMD was determined using dual energy X-ray absorptiometry (DXA); the level of vitamin D, OC and b-CrossLaps in blood serum — by enzyme immunoassay.Results and discussion. A decrease in BMD was statistically significantly more common in patients with SSc (46, 71%), than in controls (11, 31%). Significant risk factors for OP in SSc were early menopause, low physical activity, hypovitaminosis D, and probably high activity and duration of the disease. In patients with SSc, there was a significant decrease in the level of OC compared with the controls; in patients with a reduced BMD, the content of OC was significantly less than in patients with normal BMD. The average values of b-CrossLaps in the main and control groups were comparable, but in patients with OP this parameter was lower than in those with normal BMD.Conclusion. In patients with SSc, OP develops statistically significantly more often than in healthy individuals. Risk factors for OP are early menopause, low physical activity, long duration and high activity of SSc. The predominance of bone formation impairment over bone resorption as a mechanism for the development of secondary OP was noted.

Adipose, muscle, and bone tissues modulate the metabolic state of mammals. However, the role of bone tissue as a metabolic state modulator in sows has not been studied. During the gestation–lactation transition, sows undergo metabolic adaptations to meet their nutritional requirements. Among these adaptations, bone remodeling is characterized by the synthesis and inhibition of hormones that participate, together with hormones from other tissues, in fetal development and lactogenesis. Osteocalcin is a hormone synthesized by the bone tissue which has been associated in different biological models with the improvement of the metabolic state. However, in sows, published results on the concentration of osteocalcin are scarce, and its concentration throughout the reproductive cycle is unknown. Therefore, with information from published trials on the measurement of serum osteocalcin, a structured review was conducted under the following objectives: (1) to review the promising effect of osteocalcin on energy metabolism in different models and (2) to characterize and model the serum concentrations of osteocalcin during the reproductive cycle of the sow. According to the review, the results obtained for humans and other animal models suggest that osteocalcin regulates energy metabolism, which has been associated with the need for integrated metabolism to cope with the metabolic demand during gestation and lactation in mammals. If these effects are significant in the sow, current recommendations for dietary balance should be reconsidered, particularly during the gestation–lactation transition period. According to mathematical modeling, it was the period in which the lowest concentration of osteocalcin was found. [J Adv Vet Anim Res 2022; 9(4.000): 634-648]

Background: In many areas of the globe, chronic kidney disease (CKD) is a widespread health concern defined by the progressive loss of kidney function. The genetic contribution to the development of kidney disease is essential in forecasting risk variables and resolving genetic enigmas. Objective: Genetic variations are among the factors that might be linked with renal disease development. This research aims to examine the relationship between five single nucleotide polymorphisms (SNPs): rs1126616, rs35068180, rs1800247, rs4236, and rs2248359 with the risk of developing CKD among Iraqi patients. Methods: A study involved 80 subjects, divided into fifty CKD patients and thirty healthy subjects. Genotyping was identified by applying the polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) method. Results: Compared to the control group, the recurrences of the genotyping TT (p = 0.01) and their allelic T (p = 0.02) in the rs1126616 were considerably higher in the CKD group. Regarding of rs1800247 CT and TT genotypes and (T) allele exhibited a substantial excess in the CKD patients (p = 0.01, 0.0229, < 0.03, respectively). For rs4236, the TT genotype (p = 0.01) and T (p = 0.02) allele were significantly increased in the CKD patients. The recurrences of the genotyping TT (p = 0.02) and their allelic T (p = 0.01) in the rs2248359 were considerably greater in the CKD group. Furthermore, the genotypes and alleles of rs35068180 showed no significant variations among CKD patients and healthy subjects. Conclusion: the results demonstrated that four genetic polymorphisms are probably biomarkers or effective participants linked to CKD patients. Also, specific genetic polymorphisms might lower or raise a patient's renal disease risk. Differences in genetic and allelic patterns can significantly impact how a disease is treated and what medicines are used. [ J Adv Biotechnol Exp Ther 2022; 5(3.000): 687-701]

Yu-Jie Wang,1,&ast; Chun-Hua Jin,2,&ast; Jiang-Feng Ke,1 Jun-Wei Wang,1 Yi-Lin Ma,1 Jun-Xi Lu,1 Mei-Fang Li,3 Lian-Xi Li1 1Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, People’s Republic of China; 2Department of Endocrinology and Metabolism, Shanghai Songjiang District Central Hospital, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Preparatory Stage), Shanghai, People’s Republic of China; 3Department of Emergency, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei-Fang Li, Department of Emergency, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86 18930170426, Email 15821955054@126.com Lian-Xi Li, Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86 21 64369181x58337, Email lilx@sjtu.edu.cnPurpose: The association between serum osteocalcin (OCN) levels and metabolic dysfunction-associated fatty liver disease (MAFLD) is still controversial. Moreover, few studies have explored their relationship in type 2 diabetes mellitus (T2DM) patients so far. The present study aimed to investigate the association of serum OCN levels with MAFLD in Chinese T2DM patients.Methods: This cross-sectional, real-world study included 1889 Chinese T2DM inpatients. MAFLD was diagnosed by abdominal ultrasonography. Participants were divided into four groups according to serum OCN quartiles, among which the clinical characteristics were compared. The association of serum OCN levels with the presence of MAFLD was also analyzed in subjects.Results: After controlling for sex, age, and diabetes duration, the prevalence of MAFLD significantly decreased across the serum OCN quartiles (55.3%, 52.0%, 48.6%, and 42.1% for the first, second, third, and fourth quartiles, respectively, P < 0.001 for trend). A fully adjusted multiple logistic regression analysis showed that serum OCN levels were independently and negatively associated with the presence of MAFLD in T2DM patients (odds ratio, 0.832; 95% confidence interval, 0.719– 0.962; P = 0.013). Furthermore, there were significant decreases in HOMA-IR (P = 0.001 for trend) and C-reactive protein (P < 0.001 for trend) levels across the serum OCN quartiles after controlling for sex, age, and diabetes duration.Conclusion: Serum OCN levels were independently and negatively associated with the presence of MAFLD in Chinese T2DM patients, partially due to the improvement of insulin resistance and inflammation mediated by OCN. Serum OCN may be used as a biomarker to assess the risk of MAFLD in T2DM patients.Keywords: diabetes mellitus, type 2, metabolic dysfunction-associated fatty liver disease, osteocalcin, insulin resistance, inflammation

Abstract Purpose The purpose of this study was to investigate serum undercarboxylated osteocalcin (ucOC) levels in partially edentulous patients scheduled to receive implant treatment and determine the association between ucOC levels, vegetable intake, vitamin K, dietary fiber intake, and functional tooth number in the posterior region (p-FTN). Methods A total of 46 patients (20 male and 26 female, 61.9 ± 12.7 years old) were included. The association among serum ucOC levels, vegetable intake, vitamin K and dietary fiber intake was assessed using Spearman’s rank correlation coefficient and binary logistic regression analysis. Results In total, 35% of patients (16/46 subjects) showed an abnormally high ucOC level (≧ 4.5 ng/mL). p-FTN showed a weak positive correlation with vegetable intake, vitamin K and dietary fiber intake (r = 0.28, 0.21, and 0.14, respectively) and a significant negative correlation with ucOC levels (r = − 0.51). Multivariate analysis demonstrated that p-FTN as well as vitamin K intake showed a significant negative association with serum ucOC levels. Conclusions More than one-third of patients showed abnormally high ucOC levels. p-FTN showed a negative association with serum ucOC levels, which indicated the possibility that oral status affected bone quality.

Osteoporosis is a systematic bone disorder characterized by bone mass loss and bone tissue architectural degeneration. The incidence of osteoporosis in women increases with age, reflecting the considerable increase in bone loss rate in postmenopausal women once estrogen loses its protective influence. The purpose of this study was to determine the levels of Osteocalcin, Vitamin D, and other parameters that influence bone quality and increased bone fragility in postmenopausal Iraqi women with type 2 diabetes mellitus (T2DM). The levels of vitamin D receptor and vitamin D binding protein in serum are studied for the first time in our study. The present study included 89 postmenopausal women aged 50-70 years old, 62 T2DM patients, and 27 controls. Ten of the T2DM patients were considered osteoporotic, 28 were considered osteopenia, and 22 were normal; this classification is according to the WHO criterion. After matching for body mass index (BMI) and age for patients and controls, results show a significant difference in serum Osteocalcin, vitamin D, and vitamin D binding protein levels in patients compared to controls. In our study, diabetic patients appear with high levels of Osteocalcin, vit.D, and vitamin D binding protein compared with non-diabetic control. The processes underlying diabetes mellitus-induced skeletal problems are unknown. Anti-diabetic medications might have an adverse or favorable effect on bone metabolism. The study concludes that managing skeletal health in postmenopausal women entails screening fracture risk factors, lowering modifiable risk variables through dietary and lifestyle modifications, and using a pharmacologic treatment for individuals at high risk of osteoporosis or fracture. Women with osteoporosis must be managed for the rest of their lives.

Background and objective: Graphene quantum dots (GQDs), a type of carbon-based nanomaterial, have remarkable biological, physical, and chemical properties. This study investigated the biological mechanisms of the proliferation and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) induced by GQDs in an inflammatory microenvironment. Materials and methods: PDLSCs were cultured in osteogenic-induced medium with various concentrations of GQDs in standard medium or medium mimicking a proinflammatory environment. The effects of GQDs on the proliferation and osteogenic differentiation activity of PDLSCs were tested by CCK-8 assay, Alizarin Red S staining, and qRT‒PCR. In addition, Wnt/β-catenin signalling pathway-related gene expression was measured by qRT‒PCR. Results: Compared with the control group, the mRNA expression levels of ALP, RUNX2, and OCN and the number of mineralized nodules were all increased in PDLSCs after treatment with GQDs. Moreover, during the osteogenic differentiation of PDLSCs, the expression levels of LRP6 and β-catenin, which are Wnt/β-catenin signalling pathway-related genes, were upregulated. Conclusion: In the inflammatory microenvironment, GQDs might promote the osteogenic differentiation ability of PDLSCs by activating the Wnt/β-catenin signalling pathway. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the socket healing outcome after alveolar ridge preservation at infected molar sites using an erbium-doped yttrium aluminium garnet (Er:YAG) laser. Methods: Eighteen patients who needed molar extraction and exhibited signs of infection were included and allocated into either the laser group or the control group. Er:YAG laser irradiation for degranulation and disinfection was performed with alveolar ridge preservation (ARP) in the laser group. Traditional debridement with a curette was performed in the control group. Two months after ARP, bone tissue samples were harvested at the time of implant placement for histological analysis. Assessment of dimension changes in alveolar bone was conducted by superimposing two cone-beam computed tomography (CBCT) scans taken at baseline and two months after extraction. Results: Histologically, after two months of healing, Er:YAG laser treatment resulted in more newly formed bone (laser: 17.75 ± 8.75, control: 12.52 ± 4.99, p = 0.232). Moreover, greater osteocalcin (OCN) positive expression and lower runt-related transcription factor 2 (RUNX-2) positive expression were detected in the laser group. However, no statistically significant difference was observed between the two groups. The difference in the vertical resorption of the buccal bone plate was statistically significant between groups (laser: -0.31 ± 0.26 mm, control: -0.97 ± 0.32 mm, p < 0.05). Major changes in ridge width were observed at 1 mm below the bone crest. However, the differences between groups were not significant (laser: -0.36 ± 0.31 mm, control: -1.14 ± 1.24 mm, p = 0.171). Conclusions: ARP with Er:YAG laser irradiation seemed to improve bone healing by regulating osteogenesis-related factor expression in the early stage at infected sites. Trial registration: The trial was registered on the Chinese Clinical Trial Registry Platform (https://www.chictr.org.cn/) (registration number: ChiCTR2300068671; registration date: 27/02/2023). [ABSTRACT FROM AUTHOR]

Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti‐osteoporosis treatment, might protect muscle wasting independent of ucOC. We hypothesize that the combination of ucOC and ibandronate (IBN) treatments has superior protective effects against immobilization‐induced muscle wasting and insulin resistance than either treatment alone. C57BL/6J mice were hindlimb‐immobilized for two weeks, with injections of vehicle, ucOC (90 ng/g daily) and/or IBN (2 μg/g weekly). Insulin/oral glucose tolerance tests (ITT/OGTT) were performed. Immediately after immobilization, muscles (extensor digitorum longus (EDL), soleus, tibialis anterior, gastrocnemius and quadriceps) were isolated and measured for muscle mass. Insulin‐stimulated glucose uptake (EDL and soleus) was examined. Phosphorylation/expression of proteins in anabolic/catabolic pathways were examined in quadriceps. Primary human myotubes derived from older adult muscle biopsies were treated with ucOC and/or IBN, then signalling proteins were analysed. Combined treatment, but not individual treatments, significantly increased the muscle weight/body weight ratio in immobilized soleus (31.7%; P = 0.013) and quadriceps (20.0%; P = 0.0008) muscles, concomitant with elevated p‐Akt (S473)/Akt ratio (P = 0.0047). Combined treatment also enhanced whole‐body glucose tolerance (16.6%; P = 0.0011). In human myotubes, combined treatment stimulated greater activation of ERK1/2 (P = 0.0067 and 0.0072) and mTOR (P = 0.036), and led to a lesser expression of Fbx32 (P = 0.049) and MuRF1 (P = 0.048) than individual treatments. These findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. Key points: It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism.Bisphosphonates, an anti‐osteoporosis treatment, might protect against muscle wasting independent of ucOC.The combination treatment of ucOC and ibandronate was shown to exert a greater therapeutic effect against immobilization‐induced muscle wasting, and led to greater activation of anabolic pathway and less expression of catabolic signalling proteins in myotubes derived from older adults, compared with individual treatments.The combination treatment was found to improve whole‐body glucose tolerance.Our findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. [ABSTRACT FROM AUTHOR]

Purpose: Microcalcification (MC) is a valuable diagnostic indicator to detect invasive breast cancer (IBC). This study aimed to determine the clinicopathological features of IBC with MC and detect biomarkers related to the potential mechanism of the MC formation in IBC. Methods: Data from 364 patients with IBC were collected for the clinical characteristic analysis. The analysis of clinical data helped us to establish a predictive model of axillary node metastasis (ANM) before surgery. In addition, 49 tissue samples of IBC patients were collected to test the protein levels of osteocalcin (OCN) and hypoxia-inducible factor-1a (HIF-1a) by immunohistochemistry. Results: Significant differences were observed in tumor size, age, ANM, HER2+, TNM stage, and mutant P53 between samples from IBC patients with MC and samples from IBC patients without MC. Younger age, a larger tumor size, a higher number of childbirths, and MC were independent predictors for ANM in IBC. HIF-1a protein level was higher in tumor tissue than in normal tissue. High protein levels of OCN and HIF-1a are related to the complication of MC in IBC. Of the patients that exhibited high HIF-1a protein levels, the percentage of high OCN protein levels was larger in patients with ANM. Conclusion: Based on this study, we concluded that patients with MC had a comparatively poor prognosis. MC was an independent predictive factor associated with the risk of ANM. High protein levels of OCN and HIF-1a were associated with MC and ANM, which were also related to poor prognosis. OCN and HIF-1a had a positive correlation in IBC. [ABSTRACT FROM AUTHOR]

Background: Regular physical activity and proper nutritional intake are crucial for bone health. However, it is unclear if this health benefit is maintained after the removal of these stimuli. This study investigated the combined effects of aerobic dance exercise and honey supplementation, followed by their subsequent cessation on bone metabolism markers and antioxidant status in females. Methods: Forty-eight young female college students were assigned into four groups: i) 16S (16 weeks of sedentary activity); ii) 8Ex8S (8 weeks of exercise followed by 8 weeks of sedentary activity); iii) 8H8S (8 weeks of honey supplementation followed by 8 weeks of sedentary activity) and iv) 8ExH8S (8 weeks of combined exercise and honey supplementation followed by 8 weeks of sedentary activity). Blood samples were collected from the participants prior to the intervention, at week 8 and at week 16 for the analysis of bone metabolism markers and antioxidant status. Results: At the mid test, bone speed of sound (SOS) (P < 0.01), serum alkaline phosphatase (ALP) (P < 0.001) and serum osteocalcin (P < 0.01) were significantly higher in the 8ExH8S group as compared to 16S group. After 8 weeks of cessation of exercise and honey supplementation, bone SOS was also significantly higher (P < 0.001) in the 8ExH8S group as compared to 16S group. In addition, the serum total calcium (P < 0.001), serum ALP (P < 0.01), total antioxidant status (TAS) (P < 0.01) and glutathione (GSH) (P < 0.01) in the 8ExH8S group were significantly higher at the post-test as compared to their respective pre-test values. Conclusion: These findings demonstrate that there was improved maintenance of the beneficial effects induced by 8 weeks of combined exercise and honey supplementation on bone properties and the antioxidant status after 8 weeks of cessation of exercise and honey supplementation as compared to exercise and honey supplementation alone. [ABSTRACT FROM AUTHOR]

Vitamin D plays an essential role in neonatal skeletal development and maternal weight gain during pregnancy. We aim to study the association between vitamin D status, maternal weight, and materno-neonatal bone metabolism parameters. From January to June 2017, we conducted this cross-sectional study among 103 pregnant women (21–42 years old) and their singletons. The levels of serum 25-(OH)D, PTH, P1NP, OC, and CTX were measured for mothers and neonates (cord blood). Serum vitamin D and OC were measured using chemiluminescence and two-site immunoradiometric assay, respectively. Meanwhile, P1NP, CTX, and PTH were measured by ELISA. The average serum vitamin D levels from mothers were 15.1 ng/mL during pregnancy and 16.2 ng/mL in the umbilical cord. At baseline, vitamin D deficient mothers were more likely to have higher PTH (36.4 vs. 18 pg/mL; p=0.029) and lower P1NP levels (90 vs. 92.5 ng/mL; p=0.026). Also, vitamin D deficient status was associated with lower fetal weight (3,293 vs. 3,358 g; p=0.019). Maternal weight was significantly correlated with P1NP (65.86 vs. 109.35; p=0.001) and OC (14.52 vs. 18.24; p=0.038), as well as cord vitamin D level (13.31 vs. 18.46; p=0.039) among normal vs. overweight women. No significant differences were found for the correlation between maternal weight and fetal parameters except for fetal weight which significantly increased with the increase in maternal weight (overweight vs. obese women=3,280 vs. 3,560; p=0.06). Maternal vitamin D status is associated with maternal and neonatal bone metabolism parameters as well as maternal and neonatal weight. [ABSTRACT FROM AUTHOR]

Bone defects (BDs), a prevalent clinically refractory orthopaedic disease, presently have no effective treatments. Mesenchymal stem cells (MSCs) can differentiate into osteoblasts and serve as potential seed cells for bone tissue engineering for BD treatment. However, the feasibility of using MSCs as seed cells for bone tissue engineering remains unclear. As a result, the critical issue of large‐scale cell‐scaffold preparation remains unresolved. In this study, we demonstrated for the first time that human embryonic stem cell‐derived MSCs, also known as immunity‐and‐matrix‐regulatory cells (IMRCs), could be inoculated into microcarriers to create osteogenic micro‐tissues appropriate for scalable production in 250 mL bioreactor. IMRCs were generally smaller than umbilical cord‐derived MSCs (UCMSCs) and could attach, migrate, proliferate and differentiate within the porous microcarriers, whereas UCMSCs could only attach to the surface of microcarriers. Osteogenic micro‐tissues generated from IMRCs‐seeded microcarriers significantly increased osteocalcin levels after 21 days of differentiation in a bioreactor. Furthermore, the expression levels of osteogenic biomarker genes/proteins such as alkaline phosphatase (ALP), osteocalcin (OCN), runt‐related transcription factor 2 (RUNX2), osteopontin (OPN) and osterix (OSX) were significantly higher than osteogenic micro‐tissues derived from UCMSCs‐seeded microcarriers. Our findings imply that IMRCs could potentially serve as seed cells for the scalable production of osteogenic micro‐tissues for BD treatment. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effects of intermittent parathyroid hormone on cementoblast‐mediated periodontal repair in the context of orthodontic‐induced root resorption. Materials and Methods: The rat model of orthodontic‐induced root resorption was established. Sixty rats were randomly allocated into the experiment group (n = 30) and the control group (n = 30), either receiving a daily subcutaneous injection of recombinant human PTH or placebo vehicle. Enzyme‐linked immunosorbent assay, Micro‐computed tomography, hematoxylin and eosin staining, and immunohistochemistry staining were performed to detect the periodontal repair. In vitro, OCCM‐30 cells were exposed to intermittent PTH (incubated with PTH for the first 6 h in each 24‐h cycle). After three cycles, flow cytometry assay, alkaline phosphatase staining, and Alizarin red staining were performed. Quantitative real‐time polymerase chain reaction and Western blotting were employed to further determine the effects of intermittent PTH. Results: Intermittent PTH‐responsive repair enhancement was detected with the expression of bone sialoprotein, osteocalcin, collagen‐1, and alkaline phosphatase significantly upregulated. Increased expressions of cementoblastic proteins were positively correlated to cycles of PTH administration. The proportion of cementoblasts in S and G2/M phases was increased; namely, intermittent PTH promoted cementoblast cell proliferation. Conclusions: Intermittent parathyroid hormone administration promotes cementoblast‐mediated cementogenesis during periodontal repair in a time‐dependent manner. [ABSTRACT FROM AUTHOR]

The use of biomaterial for tissue repair involves the interaction between materials and cells, and the coagulum formation represents the first step of tissue healing. This process is particularly critical in the oral cavity, where the wounds are immediately subjected to the masticatory mechanical stress, saliva invasion, and bacterial attack. Therefore, the present study aimed to explore the structural features and the biological activities of a hemostatic collagen sponge on human gingival fibroblasts (HGFs) and human oral osteoblasts (HOBs). The microstructure of the collagen sponge was characterized by a scanning electron microscope (SEM) and histological analysis. The porosity was also calculated. To investigate biological activities, HGFs and HOBs were cultured on the collagen sponges, and their adhesion was observed at SEM on the third day, while cell viability was investigated at the third and seventh days by Tetrazolium (MTT) assay. For osteoblasts seeded on collagen sponge the mineralization ability was also evaluated by alkaline phosphatase (ALP) assay at the seventh day, and by Alizarin red staining on the 14th. Furthermore, the gene expression of ALP and osteocalcin (OCN) was investigated after 3, 7 and 14 days. SEM images of the sponge without cells showed a highly porous 3D structure, confirmed by the measurement of porosity that was more than 90%. The samples cultured were characterized by cells uniformly distributed and adhered to the sponge surface. Proliferation ended up being promoted, as well as the mineralization ability of the osteoblasts, mainly at the mature stage. In conclusion, this collagen sponge could have a potential use for tissue healing. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the effects of supervised cycling sprint interval training (SIT) on serum osteocalcin, lipocalin-2 and sclerostin levels, and bone mineral characteristics among obese adolescent boys. Untrained obese adolescent boys aged 13.4 ± 0.3 were assigned to either a 12-week SIT group (3 sessions/week), or a non-exercising control group who continued with their habitual everyday life. Serum osteocalcin, lipocalin-2 and sclerostin concentrations, and bone mineral values were assessed before and after intervention. After 12-week intervention, where 14 boys in both groups ended the study, there were no significant differences in serum osteokine levels between the groups after 12 weeks, while whole body bone mineral content and lower limb bone mineral density increased in the SIT group (p < 0.05). Change in body mass index was negatively correlated with the change in osteocalcin (r = −0.57; p = 0.034), and positively correlated with the change in lipocalin-2 levels (r = 0.57; p = 0.035) in the SIT group. Supervised 12-week SIT intervention improved bone mineral characteristics, but did not change osteocalcin, lipocalin-2 or sclerostin levels in adolescent boys with obesity. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, it is difficult for a single scaffold material to meet the needs of osteogenesis in bone tissue engineering. Microsphere scaffolds combined with a variety of materials can maximize their strengths and avoid their weaknesses, which has great application potential. OBJECTIVE: To explore the biocompatibility, degradability, and osteoinductivity of a new type of polytrimethylene carbonate/β-tricalcium phosphate in animals. METHODS: The β-tricalcium phosphate bone cement and polytrimethylene carbonate/β-tricalcium phosphate microsphere scaffold were prepared. Eighteen male SD rats were randomly divided into three groups (n=6) according to their weight. No material was implanted in the bilateral femoral defects in the blank control group. The β-tricalcium phosphate bone cement was implanted in the bilateral femoral defects in the control group. Polytrimethylene carbonate/ β-tricalcium phosphate microsphere scaffold was implanted at bilateral femoral defects in the experimental group. At 4, 8, and 12 weeks after operation, the bilateral femurs were taken out for hematoxylin-eosin staining, Masson staining, and immunohistochemical staining for osteocalcin. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining and Masson staining: At 4 weeks after operation, the bone defect in the blank control group was surrounded by fibrous tissue and numerous inflammatory cells gathered. In the control group, the material was mostly degraded and surrounded by fibrous tissue, with a small amount of new bone matrix and bone trabecular formation at the edge of the material, which was surrounded by a few inflammatory cells. The material in the experimental group did not degrade remarkably and was surrounded by fibrous tissue. Some new bone matrix and bone trabecular formation were detected at the edge of the material, which was surrounded by a few inflammatory cells. At 12 weeks postoperatively, the blank control group presented regular trabecular bone, which was connected to each other, without inflammatory cells. In the control group, the material was completely degraded and trabecular bone was regular, forming a thick lamellar shape, without inflammatory cells. In the experimental group, materials were partially degraded; bone mass was increased and dense, with the absence of inflammatory cells. (2) Immunohistochemical staining: With prolonged time, the expression of osteocalcin in the bone defect of the control group increased first and then decreased. The expression of osteocalcin in the blank control group and the experimental group showed a gradually increasing trend. The expression of osteocalcin at each time point was higher in the control and experimental groups than that of the blank control group (P < 0.05). The expression of osteocalcin in the experimental group was higher than that of the control group at 12 weeks postoperatively (P < 0.05). (3) These findings exhibit that the polytrimethylene carbonate/β-tricalcium phosphate microsphere scaffold has good biocompatibility, osteoinductivity, and moderate biodegradability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have confirmed that miR-27b at the lipid level can control multiple genes that have an important impact on dyslipidemia. It is speculated that miR-27b may function in osteoporosis by targeting peroxisome proliferators-activated receptors γ2 (PPARγ2). OBJECTIVE: To investigate the effect of miR-27b/PPARγ2 axis in the dexamethasone-induced osteoporosis model in mouse embryonic osteogenic precursor cells MC3T3-E1 and related mechanisms of action. METHODS: After MC3T3-E1 cells were dexamethasone-induced and cultured in vitro, miR-27b mimic, miR-27b inhibitor, NC-mimic, NC-inhibitor, siPPARγ2, and siNC were transfected with Lipofectamine®2000, and dimethyl sulfoxide was used as a control. After the cells were induced and cultured, the cell viability and alkaline phosphatase activity were detected to determine the osteogenesis and differentiation levels of the cells. The mRNA and protein expression levels of osteogenic differentiation genes miR-27B, PPARγ2, Runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2 and osteocalcin were detected by real-time fluorescence quantitative PCR and western blot methods. Bioinformatics analysis predicted the downstream target genes of miR-27b followed by verification with dual luciferase gene reporter experiments. RESULTS AND CONCLUSION: Dexamethasone treatment significantly reduced cell viability and miR-27b expression levels in MC3T3-E1 pre-osteoblasts. Compared with dimethyl sulfoxide, dexamethasone significantly inhibited MC3T3-E1 cell viability and downregulated miR-27b expression levels at 24 and 48 hours. miR-27b could directly regulate PPARγ2. Compared with the corresponding NC-mimic, the miR-27b mimic significantly upregulated the expression level of miR-27b, while the miR-27b inhibitor significantly downregulated the expression level of miR-27b. Furthermore, PPARγ2 miRNA and protein expression levels were inhibited by the miR-27b mimic and significantly enhanced by the miR-27b inhibitor. miR-27b overexpression attenuated the inhibitory effect of dexamethasone on the proliferation and osteogenic differentiation of MC3T3-E1 pre-osteoblasts. Dexamethasone significantly inhibited osteoblast differentiation compared with the dimethyl sulfoxide + NC-mimic group. In contrast, the dexamethasone-mediated inhibition was reversed by the miR-27b mimic. Cellular alkaline phosphatase activity and bone morphogenetic protein 2, Runx2 and osteocalcin protein expression levels were partially restored. Inhibition of miR-27b suppressed proliferation and osteogenic differentiation of MC3T3-E1 pre-osteoblasts through the upregulation of PPARγ2. Knockout of miR-27b significantly increased PPARγ2 expression and decreased cell viability, osteoblast differentiation, alkaline phosphatase activity, and expression levels of bone morphogenetic protein 2, Runx2 and osteocalcin. PPARγ2 may be a direct target of miR-27b. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoblasts and osteoclasts play an important role in bone remodeling through the release of regulatory factors to remain the bone homeostasis. When the balance between functions and activities of the two types of cells is disturbed, bone diseases such as osteoporosis and osteoarthritis will occur. Sambucus adnata Wall. is commonly used by the ethnic Yi people to treat injuries caused by falls and fractures. Our previous studies have found that the water extract (SAW-A) and dichloromethane extract (SAW-B) of Sambucus adnata Wall. can promote fracture healing and improve osteoporosis in the active parts of fractures. However, their effects on osteoblast proliferation and differentiation in the active parts are still unclear. OBJECTIVE: To investigate the biological effects of SAW-A and SAW-B extracts from Sambucus adnata Wall. on the proliferation and differentiation of osteoblasts. METHODS: Osteoblasts were extracted from the skull of newborn Sprague-Dawley rats by collagenase digestion, and cell counting kit-8 was used to detect the cytotoxicity of SAW-A and SAW-B. The proliferation activity of osteoblasts was detected by cell counting kit-8 at 24, 48, and 72 hours after extract intervention, to investigate the effects of 312.5 mg/L SAW-A and 156.15 mg/L SAW-B on osteoblast proliferation. Flow cytometry was used to detect the effect of SAW-A and SAW-B on cell activity at 6 days of intervention. The proliferation and differentiation of osteoblasts after SAW-A and SAW-B intervention were detected by alkaline phosphatase staining and alizarin red staining. Real-time fluorescence quantitative PCR assay was performed to detect the relative expression of osteogenesis-related genes RUNX2, bone sialoprotein, osteocalcin and type I collagen A1. RESULTS AND CONCLUSION: SAW-A and SAW-B could significantly improve the proliferation of osteoblasts at 48 and 72 hours after intervention, and SAW-B was stronger than SAW-A. Flow cytometry results showed that SAW-A and SAW-B inhibited apoptosis in osteoblasts after 6 days of intervention. The results of alkaline phosphatase and alizarin red staining showed that SAW-A and SAW-B could promote osteoblast mineralization. The relative expression levels of RUNX2, bone sialoprotein, osteocalcin and type I collagen A1 increased, and SAW-B showed a better effect on the expression of bone sialoprotein and type I collagen A1 than SAW-A. To conclude, SAW-A and SAW-B can both promote osteoblast differentiation. [ABSTRACT FROM AUTHOR]

Simple Summary: Fatty liver hemorrhage syndrome is one of the main metabolic diseases in laying hens, which leads to lipid accumulation, fragile liver, rupture bleeding, and sudden death. Osteocalcin, a kind of noncollagenous protein, has recently been found to protect chickens from the disease. However, the most studies have focused on the use of osteocalcin in mammals. In this review, we try to outline the functions of osteocalcin in fatty liver hemorrhage syndrome in poultry based on the recent outcomes. Osteocalcin (OCN) is synthesized and secreted by differentiating osteoblasts. In addition to its role in bone, OCN acts as a hormone in the pancreas, liver, muscle, fat, and other organs to regulate multiple pathophysiological processes including glucose homeostasis and adipic acid metabolism. Fat metabolic disorder, such as excessive fat buildup, is related to non-alcoholic fatty liver disease (NAFLD) in humans. Similarly, fatty liver hemorrhage syndrome (FLHS) is a metabolic disease in laying hens, resulting from lipid accumulation in hepatocytes. FLHS affects hen health with significant impact on poultry egg production. Many studies have proposed that OCN has protective function in mammalian NAFLD, but its function in chicken FLHS and related mechanism have not been completely clarified. Recently, we have revealed that OCN prevents laying hens from FLHS through regulating the JNK pathway, and some pathways related to the disease progression have been identified through both in vivo and vitro investigations. In this view, we discussed the current findings for predicting the strategy for using OCN to prevent or reduce FLHS impact on poultry production. [ABSTRACT FROM AUTHOR]

BACKGROUND: Many studies have found that the pathological progression of steroid-induced osteonecrosis of the femoral head is related to abnormal proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells, in which a disintegrin and metalloproteases 10 (ADAM10) is highly involved, but the specific mechanism remains unclear. OBJECTIVE: To investigate the effects of ADAM10 on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells derived from steroidinduced osteonecrosis of the femoral head patients and its possible mechanism. METHODS: Bone marrow was harvested from proximal femur in 23 patients with steroid-induced osteonecrosis of the femoral head and 17 patients with femoral neck fracture under sterile conditions. Bone marrow mesenchymal stem cells from steroid-induced osteonecrosis of the femoral head (S-BMSCs) and femoral neck fracture (F-BMSCs) were isolated by density gradient centrifugation, and cultured to the third generation in vitro. The proliferation activity of cells in the two groups was detected by CCK-8 assay. Alizarin red staining and alkaline phosphatase staining were used to observe the osteogenic differentiation ability of cells in the two groups. qRT-PCR and western blot assay were used to detect the levels of ADAM10 mRNA and protein in cells of the two groups. S-BMSCs were infected with ADAM10 overexpression lentivirus vector, and then treated with Notch signaling pathway inhibitor DAPT. The proliferation activity of these cells was detected by CCK-8 assay. Alizarin red staining and alkaline phosphatase staining were used to observe the osteogenic differentiation of cells. qRT-PCR was used to detect the expression levels of osteogenic markers alkaline phosphatase, Runt-related transcription factor 2, and osteocalcin mRNA. The expression levels of Notch signaling pathway related proteins Notch1, NICD, and Hes1 were detected by western blot assay. RESULTS AND CONCLUSION: (1) The proliferation activity, osteogenic differentiation ability and the expression level of ADAM10 in S-BMSCs were significantly lower than those in F-BMSCs (P < 0.01). (2) After ADAM10 overexpression, the proliferation activity, osteogenic differentiation ability, the expression levels of alkaline phosphatase, Runt-related transcription factor 2, and osteocalcin mRNA and Notch1, NICD and Hes1 protein of S-BMSCs were significantly increased (P < 0.05). However, combined intervention with DAPT significantly inhibited the promoting effects of ADAM10 overexpression on proliferation activity and osteogenic differentiation ability of S-BMSCs, and inhibited the activation of Notch signaling pathway. (3) The results show that ADAM10 can be underexpressed in S-BMSCs, and its overexpression can enhance the proliferation and osteogenic differentiation ability of S-BMSCs, and its mechanism may be related to the activation of Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: Osteocalcin (OC) and its effect on insulin resistance in animals have been studied and demonstrated. But, the same is yet to be established in humans. Moreover, the association of Gestational Diabetes Mellitus (GDM) with serum Osteocalcin (OC) levels hasn't been studied much and hence, is an area of scope for research. This study is aimed at assessing the difference between serum OC levels in non-diabetic pregnant women (Group I - Controls) and women diagnosed with GDM (Group II - Cases) and determine whether they can be used in early prediction of GDM. Methods: A thorough and systematic search of PUBMED and SCOPUS databases was done to identify relevant articles, using the keywords Osteocalcin, pregnancy, diabetes and gestational diabetes. Studies which had included atleast 10 study participants per group and had measured serum OC levels in various forms viz., undercarboxylated Osteocalcin (ucOC), N terminal Mid fragment Osteocalcin (N MID OC) and total Osteocalcin (tOC) were considered relevant. Out of 45 studies, 9 studies were selected for the present study. Results: There was no significant difference in the mean ucOC and N MID OC levels between the GDM and nondiabetic controls, whereas, a significant difference was found in the tOC levels between the two groups. Conclusion: Thus, this meta-analysis shows that tOC may be used as potential marker for GDM rather than ucOC and N MID OC. [ABSTRACT FROM AUTHOR]

Uncarboxylated osteocalcin (GluOC), a small-molecule protein specifically synthesized and secreted by osteoblasts, is important in the regulation of energy metabolism. In our previous study, GluOC was shown to be effective in ameliorating dyslipidemia and hepatic steatosis in KKAy mice. However, the underlying mechanism of GluOC action on hepatocytes has not been well validated. In this study, oleic acid/palmitic acid (OA/PA)-induced HepG2 and NCTC 1469 cells were used as non-alcoholic fatty liver disease (NAFLD) cell models, and triacylglycerol (TG) levels were measured by oil red O staining, Nile Red staining, and ELISA. The fatty acid synthesis-related protein expression was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. The results show that GluOC reduced triglyceride levels, and decreased the expression of sterol regulatory element-binding protein-1c (SREBP-1c) and stearyl-coenzyme A desaturase 1 (SCD1). si-SCD1 mimicked the lipid accumulation-reducing effect of GluOC, while overexpression of SCD1 attenuated the effect of GluOC. In addition, GluOC activated AMP-activated protein kinase (AMPK) phosphorylation to affect lipid metabolism in hepatocytes. Overall, the results of this study suggest that GluOC decreases SCD1 by activating AMPK to alleviate hepatocyte lipid accumulation, which provides a new target for improving NAFLD in further research. [ABSTRACT FROM AUTHOR]