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Objectives: This study aimed to compare and correlate plasma and salivary levels of cardiometabolic risk biomarkers' of pharmacotherapy (appraised using colorimetric assays), adiposity, and atherogenicity indices. Methods: 61 Nascent MetS subjects vs. 30 lean normoglycemic and healthy controls were recruited in Family Medicine outpatient clinics/Jordan University Hospital (a referral medical center). Fasting blood and saliva specimens were collected. Clinical and anthropometric variables were determined along with atherogenecity and adiposity indices. Results: Among nascent MetS (metabolic syndrome) recruits, almost half were normoglycemic, 43% were prediabetic and 8% were diabetic. Pronouncedly Glycemic (FPG and Alc) and lipid parameters (TG, HDL-C and non-HDL-C), adiposity indices (BMI, WHR, WtHR, Conicity-index, BAI, LAP, VAI) and atherogenicity indices (AIP, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C and TG/HDL-C) were higher in the nascent MetS group (P<0.05 vs. controls). Markedly among the plasma cardiometabolic risk biomarkers (P<0.05 vs. controls) in the nascent MetS group, adipolin, cathepsin S, ghrelin, irisin, LBP, leptin, and osteocalcin were higher but plasma FGF1 levels were oddly lower. Significantly (P<0.05 vs. controls) nascent MetS -linked salivary levels of adipolin and LBP were higher as opposed to the lower cathepsin S. Only osteocalcin, amongst 9 metabolic risk biomarkers studied, had remarkably significant correlation between plasma and saliva levels, in both total sample and MetS patients (P<0.05). Markedly in the nascent MetS only group, both plasma and salivary osteocalcin correlated with FPG and A1c (P<0.05); salivary osteocalcin correlated with BMI and LAP (P<0.05). Likewise, in the total sample plasma osteocalcin correlated significantly with BMI, BAI, WHt R, SBP, DBP, TG, LAP, VAI, TG/HDL-C and AIP (P<0.05), while salivary osteocalcin had substantial correlations only with FPG and A1c (P<0.05). Conclusion: Association of nascent MetS-related plasma and salivary osteocalcin levels and clinical characteristics and indices propagate salivary osteocalcin as a non-invasive marker for clinical control of MetS-/preDM. [ABSTRACT FROM AUTHOR]

Intracanal medications are used in endodontic treatment due to their antibacterial activity and ability to induce the periapical repair. Among the intracanal medications, the Calen (CAL; SS. White, Brazil) is a calcium hydroxide-based medication that provides an alkaline pH and releases calcium, exerting an antimicrobial activity. Bio-C Temp (BIO; Angelus, Brazil), a ready-to-use bioceramic intracanal medication, was designed to stimulate the mineralized tissues formation. Here, we investigated the bioactive potential of BIO in comparison to the CAL in the rat subcutaneous. Polyethylene tubes filled with medications, and empty tubes (control group, CG) were implanted in the subcutaneous tissue of rats. After 7, 15, 30 and 60 days, the blood was collected for calcium (Ca+2) and alkaline phosphatase (ALP) measurement, and the capsules around the implants were processed for morphological analyses. The data were submitted to two-way ANOVA and Tukey test (p < 0.05). At 7, 15 and 30 days, the ALP level was grater in BIO and CAL than in CG (p < 0.0001). At 7 and 15 days, greater Ca+2 level was seen in the serum of CAL samples. From 7 to 60 days, an increase in the number of fibroblasts, osteocalcin- and osteopontin-immunolabelled cells was observed in BIO and CAL groups (p < 0.0001). In all periods, BIO and CAL specimens showed von Kossa-positive structures. Moreover, ultrastructural analysis revealed globules of mineralization in the capsules around the BIO and CAL specimens. Thus Bio-C Temp caused an increase in the ALP, osteocalcin and osteopontin, which may have allowed the formation of calcite, suggesting bioactive potential. [ABSTRACT FROM AUTHOR]

Dysregulation of osteoblastic differentiation is an important risk factor of osteoporosis, the therapy of which is challenging. Dehydrocostus lactone (DHC), a sesquiterpene isolated from medicinal plants, has displayed anti‐inflammatory and antitumor properties. In this study, we investigated the effects of DHC on osteoblastic differentiation and mineralization of MC3T3‐E1 cells. Interestingly, we found that DHC increased the expression of marker genes of osteoblastic differentiation, such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Additionally, DHC increased the expressions of collagen type I alpha 1 (Col1a1) and collagen type I alpha 2 (Col1a2). We also demonstrate that DHC increased ALP activity. Importantly, the Alizarin Red S staining assay revealed that DHC enhanced osteoblastic differentiation of MC3T3‐E1 cells. Mechanistically, it is shown that DHC increased the expression of Runx‐2, a central regulator of osteoblastic differentiation. Treatment with DHC also increased the levels of phosphorylated p38, and its blockage using its specific inhibitor SB203580 abolished the effects of DHC on runt‐related transcription factor 2 (Runx‐2) expression and osteoblastic differentiation, suggesting the involvement of p38. Based on these findings, we concluded that DHC might possess a capacity for the treatment of osteoporosis by promoting osteoblastic differentiation. [ABSTRACT FROM AUTHOR]

Study aim: This cross-sectional study examined the relationship between biological factors, physical activity (PA), bone turnover markers (BTMs) and bone mineral density (BMD) in women with subclinical hypothyroidism (SCH) and healthy. Material and methods: The study included 135 women. Bone parameters were measured by the densitometry. Calcium, phosphorus, osteocalcin (OC), total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), vitamin D and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were measured in blood serum. PA were evaluated by metabolic equivalent of task (MET). Results: Women with SCH had lower BMD in hip and lumbar spine, calcium, vitamin D and higher values of ICTP than the healthy group. In women with SCH, the affecting BMD in the femoral neck were ICTP (µg/l), (η² = 0.083), and also 25(OH)D (ng/ml), (η² = 0.080) and PA level (I/S), (η² = 0.115). BMD in the spine was affected by PA level (I/S), (η² = 0.173). The parameters affecting BMC in the femoral neck were 25(OH)D (ng/ml), (η² = 0.073). In all women sufficient levels of PA determined higher BMD. Conclusions: PA and BTMs significantly determine BMD levels. PA can be an important area of rehabilitation and physical therapy as an available measure to counteract BMD loss in postmenopausal healthy women and those with SCH. [ABSTRACT FROM AUTHOR]

Objective: Weight reduction often accompanies muscle loss. Existing studies highlight the involvement of osteocalcin (OC) in energy metabolism and its potential to prevent age-related muscle loss. Nevertheless, these studies predominantly involve individuals with hyperglycemia, yielding conflicting research outcomes. This study investigated the protective role of OC against muscle loss during weight reduction in individuals without metabolic syndrome (MetS). Measures: We enrolled 130 overweight or obese individuals without MetS in a 4-month high-protein, energy-restricted dietary weight management program conducted at two clinic centers. Body composition and laboratory tests were assessed both before and after weight loss. Correlation and regression analysis were made between the changes in metabolic indicators and muscle mass during weight loss. Results: Following weight loss, there was a decrease in body mass index (BMI), percentage of body fat (PBF), visceral fat area (VFA), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), and lipid profile, and increase in the percentage of skeletal muscle (PSM) and vitamin D. There was no change in osteocalcin (OC) during the intervention. Correlation analysis of the relative changes in all metabolic indicators revealed a positive correlation between OC and PSM (r=0.383, p=0.002). Multiple linear regression analysis found that OC has a significant protective effect on muscles during weight loss in males after adjusting for confounding factors (b=0.089, p=0.017). Conclusion: High-protein, energy-restricted diets demonstrate efficacy in enhancing metabolic indicators within the weight-loss population. Furthermore, OC exhibits a protective effect on muscle mass during weight reduction in individuals without MetS, with this effect being particularly evident in males. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the levels of bone alkaline phosphatase (BALP) and osteocalcin (OC) in the saliva of growing patients of different maturation levels. The sample consisted of 55 patients (34 females and 21 males of 7–16 years old). Two milliliters of saliva were collected and BALP and OC levels were assessed. Skeletal age was estimated using the cervical vertebral maturation method (CVM). The relationship between the biomarkers' concentration in saliva and skeletal age was examined with the Spearman's coefficient "ρ" (rho). Correlations between skeletal age groups and BALP and OC concentrations were assessed with the Kruskal–Wallis or the Mann–Whitney tests. No statistically significant differences in the levels of BALP (p = 0.568) and OC (p = 0.996) in saliva were identified according to the patient's skeletal age. The use of BALP and OC levels in saliva seems to be dubious for skeletal growth assessment. However, slightly differentiated levels of those biomarkers, especially of BALP, through the different maturation stages, with higher concentrations at the pubertal phase, have been noticed. More studies are needed to clarify the exact potential role of these biomarkers as predictors of pubertal onset. [ABSTRACT FROM AUTHOR]

Background: The past few decades have seen a marked increase in the macrovascular complications of Type-2 diabetes mellitus (T2DM) such as coronary heart disease, peripheral arterial disease, and cerebrovascular disease. This has been predominantly attributed to the increased atherosclerosis in these patients. Atherosclerosis usually remains an asymptomatic condition and this poses a significant challenge in its early diagnosis and timely intervention. Hence, there is an immediate need for exploring novel tools to aid in the early detection of atherosclerosis, especially in T2DM patients. Osteocalcin (OC), synthesized by osteoblasts, is a protein hormone found in the skeletal system. This protein is considered as a marker for bone density and in recent times has been gaining interest due to its protective role in cerebrovascular diseases(CVD). Methods: We conducted a cross-sectional study and evaluated the association between serum OC levels and atherosclerosis in 113 T2DM patients. Carotid intima-media thickness (CC-IMT) was used as an estimate of atherosclerosis and patients were divided into two groups (CC-IMT < 0.9 and ≥ 0.9). Correlation of serum OC levels and glycemic parameters and lipid profiles were studied and compared between both groups. Results: There is a significant negative correlation between the CC-IMT estimates and serum OC levels. CC-IMT also has a significant association with other biochemical parameters such as fasting blood sugar, glycated hemoglobin and high-density lipoprotein. Conclusion: Although the independent association of serum OC could not be established in the T2DM patient population, overall, the results favor low serum OC as a prognostic marker for atherosclerosis. [ABSTRACT FROM AUTHOR]

Finite mixture of regressions (FMR) are commonly used to model heterogeneous effects of covariates on a response variable in settings where there are unknown underlying subpopulations. FMRs, however, cannot accommodate situations where covariates' effects also vary according to an "index" variable—known as finite mixture of varying coefficient regression (FM‐VCR). Although complex, this situation occurs in real data applications: the osteocalcin (OCN) data analyzed in this manuscript presents a heterogeneous relationship where the effect of a genetic variant on OCN in each hidden subpopulation varies over time. Oftentimes, the number of covariates with varying coefficients also presents a challenge: in the OCN study, genetic variants on the same chromosome are considered jointly. The relative proportions of hidden subpopulations may also change over time. Nevertheless, existing methods cannot provide suitable solutions for accommodating all these features in real data applications. To fill this gap, we develop statistical methodologies based on regularized local‐kernel likelihood for simultaneous parameter estimation and variable selection in sparse FM‐VCR models. We study large‐sample properties of the proposed methods. We then carry out a simulation study to evaluate the performance of various penalties adopted for our regularized approach and ascertain the ability of a BIC‐type criterion for estimating the number of subpopulations. Finally, we applied the FM‐VCR model to analyze the OCN data and identified several covariates, including genetic variants, that have age‐dependent effects on OCN. [ABSTRACT FROM AUTHOR]

Introduction: Gremlin-1 is a peptide that functions as an antagonist to bone morphogenic proteins and is overexpressed in obesity and type 2 diabetes mellitus. Gremlin-1 has not yet been investigated in pregnancy, pregnancy-related insulin resistance or gestational diabetes mellitus (GDM). Patients and methods: Gremlin-1 levels were measured throughout the pregnancy of 58 women at high risk for GDM at the Medical University of Vienna. Furthermore, an oral glucose tolerance test, fasting insulin, fasting glucose, sex hormones, blood lipids, liver and renal parameters, and markers of bone development were evaluated at two points during pregnancy (< 20 weeks of gestation (GW), GW 24–28) and 12–14 weeks postpartum. Results: Gremlin-1 levels decreased from < 20 GW (mean = 9.2 pg/ml, SD = 8.4 pg/ml) to GW 24–28 (mean = 6.7 pg/ml, SD = 5.7 pg/ml, p = 0.033) and increased again postpartum, albeit not significantly (mean = 10.7 pg/ml, SD = 13.1 pg/ml, p = 0.339). During pregnancy, Gremlin-1 levels correlated negatively with osteocalcin and procollagen type I aminoterminal propeptide (P1NP), markers of bone health. Concerning glucose metabolism, Gremlin-1 levels were inversely related to the Insulinogenic Index at GW < 20. However, Gremlin-1 levels were not significantly different between women with normal glucose tolerance and GDM during pregnancy. Postpartum, Gremlin-1 was associated with the fatty liver index, osteocalcin levels, diastolic blood pressure and weight. Conclusion: Gremlin-1 levels decreased significantly during pregnancy. The biomarker is not related to GDM status, but correlates negatively with the Insulinogenic Index, an index related to beta cell function. Trial Registry Number ACTRN12616000924459. [ABSTRACT FROM AUTHOR]

Stimulation of neoosteogenesis is the main mechanism of osseointegration during installation of dental implants, bone tissue recession, and alveolar process augmentation in adentia. In experiments on miniature pigs, we used the technology of two-stage splitting of the ridge of the alveolar process of the mandible in combination with a xenograft that was placed between the fragments of the split bone plate. The morphology of the reparative process and the distribution of osteogenic differentiation markers in the compact and trabecular bone of the alveolar crest were studied. Signs of reparative osteogenesis were observed in the bone regenerate that had a lamellar structure, formed osteons, and foci of woven tissue. It was found that the xenograft was replaced by newly formed trabecular bone tissue. These sites were characterized by increased expression of osteocalcin and CD44. Augmentation technology through two-stage splitting provides trophic relationship of osteoprogenitor cells and is an effective method of osteogenesis stimulation in the alveolar process. [ABSTRACT FROM AUTHOR]

Aims: As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone‐derived hormone osteocalcin has been reported to be necessary to prevent anxiety‐like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin. Methods: Menopausal mouse model was induced by intraperitoneal injection of 4‐vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light–dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co‐localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis‐related proteins. Results: The VCD mice showed obvious anxiety‐like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL‐2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons. Conclusion: Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD‐induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise. [ABSTRACT FROM AUTHOR]

This study investigated whether osteocalcin (OCN) is present in osteoblast precursors and its relationship with initial phases of alveolar process formation. Samples of maxillae of 16-, 18-, and 20-day-old rat embryos (E16, E18, and E20, respectively), and 05-, 10-, and 15-day-old postnatal rats (P05, P10, and P15, respectively) were fixed and embedded in paraffin or araldite. Immunohistochemistry for osterix (Osx), alkaline phosphatase (ALP), and OCN detection was performed and the number of immunolabelled cells was computed. Non-decalcified sections were subjected to the von Kossa method combined with immunohistochemistry for Osx or OCN detection. For OCN immunolocalization, samples were fixed in 0.5% glutaraldehyde/2% formaldehyde and embedded in LR White resin. The highest number of ALP- and OCN-immunolabelled cells was observed in dental follicle of E16 specimens, mainly in basal portions of dental alveolus. In corresponding regions, osteoblasts in differentiation adjacent to von Kossa-positive bone matrix exhibited Osx and OCN immunoreactivity. Ultrastructural analysis revealed OCN immunoreactive particles inside osteoblast in differentiation, and in bone matrix associated with collagen fibrils and within matrix vesicles, at early stages of alveolar process formation. Our results indicate that OCN plays a role in osteoblast differentiation and may regulate calcium/phosphate precipitation during early mineralization of the alveolar process: [ABSTRACT FROM AUTHOR]

The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF), is a biomaterial that promotes soft tissue and bone healing. In a long bone defect rat model, the current study compares the effectiveness of bone autograft with PRF augmentation versus a standard bone graft procedure. There are two groups in this study, and the control group is limited to the post-test. There were 7 rats in each control (CG) and intervention group (IG). After the making of the autologous PRF, the intervention group received an autologous bone graft and PRF, as the control group only received a bone graft from the iliac crest. The graft was maintained for 4 weeks. Selected bone was chosen for immunohistochemistry of osteocalcin and histopathological measurement of bone healing. There was a statistically significant increase in osteocalcin expression compared to control in the cell cytoplasmic (p=0.040) and the osteoid matrix (p=0.025). Compared to the control group, there were no statistically significant increases in the nucleus's expression of osteocalcin in the intervention group (p=0.067). The intervention group had a clinically significant better histopathological score of bone healing (p=0.015). This study shows the effect of PRF as a biomaterial that can enhance the new bone formation process in the bone defect. This effect could be a result due to the fibrin mesh of PRF could protect the GF from proteolysis. The application of PRF combined with autologous bone graft could increase the expression of osteocalcin and increase the formation of new bone tissue in rats with a long bone defect model. [ABSTRACT FROM AUTHOR]

Background: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat‐containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. Methods: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non‐coding RNA X‐Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT‐qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull‐down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). Results: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF‐α‐mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST‐mediated biological effects in PDLSCs. Conclusion: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis. [ABSTRACT FROM AUTHOR]

Bone metabolism is impaired in diabetes mellitus (DM). Our objective is to evaluate the association of bone turnover markers (BTM) and vitamin D receptor (VDR) gene polymorphisms with bone mineral density (BMD) in DM type 1 (T1D) and DM type 2 (T2D).

Zi-Ye Chen,1 Jie Yang,1 Chen-Yang Tian,2 Wei Jia2 1Department of Nephrology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Vascular Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zi-Ye Chen, Department of Nephrology, Beijing Jishuitan Hospital, Capital Medical University, Xinjiekou No. 31 East Street, Xicheng District, Beijing, 100035, People’s Republic of China, Tel +86-13681058086, Email ziyechen93@126.comIntroduction: To examine the factors associated with PAD, with a specific focus on bone metabolism factors such as osteocalcin.Methods: This cross-sectional study examined factors about demographic, clinical, and laboratory parameters including bone metabolism biomarkers in hemodialysis patients. The ankle-brachial index (ABI) was measured in all patients, with PAD diagnosed as an ABI < 0.9.Results: Out of the 71 patients, PAD was found in 23 individuals. These patients had an average age of 63.5± 13.0 years, with 59.2% being male. Compared to non-PAD patients, those with PAD were older, had a lower proportion of males, and had a higher prevalence of diabetes and coronary artery disease. Among the factors related to bone metabolism, only osteocalcin exhibited a significant increase in the PAD group compared to the non-PAD group.Conclusion: PAD in patients on hemodialysis was independently linked to high levels of osteocalcin in the bloodstream, indicating the presence of bone metabolism disorders.Keywords: hemodialysis, osteocalcin, bone metabolism disorder, peripheral artery disease

Cardiovascular diseases have been the leading cause of death worldwide for a long time. Despite numerous studies on the pathogenetic mechanisms of cardiovascular diseases, there are many debatable issues. In recent years, an increasing number of scientific reports have appeared regarding the presence of common mechanisms in the deve­lopment of bone tissue and arterial calcification. One of the connecting links in this interaction is considered to be the impact of osteocalcin. Osteocalcin is a vitamin K-dependent protein of the bone matrix, synthesized by osteoblasts. The main function of osteocalcin is the synthesis of hydroxyapatites as main mineral component of bone tissue. In addition, osteocalcin has a wide range of extraosseous effects, the most studied is participation in the regulation of glycolipid and ener­gy metabolism. Research on the osteocalcin role in the development and progression of cardiovascular diseases are scarce, the available data is contradictory. For a deeper understanding of this problem, we conducted a systematic analysis of modern literature based on data from the scientific databases Medline (Pubmed), Scopus, Web of Science, Google Scholar, and Cochrane Library for 2013–2023. According to its results, osteocalcin is a potential biomarker of cardiovascular status, its increased values are associated with a potentially protective mechanism against the development of cardiovascular diseases. Contradictory views on the understanding of the pathogenetic mechanism of influence of general osteocalcin and its forms on the course of cardiovascular diseases necessitate conduction of further research.

Purpose: To assess the effect of different kinds of biomaterials placed with maxillary sinus floor augmentation (MSFA) on bone regeneration. Materials and Methods: Thirty-six New Zealand rabbits were used in the study. A standardized method of surgical approach was used for MSFA under anesthesia in all groups. The procedure was performed for each animal. Six separate groups with 12 cases were created. In group 1, no graft was used in MSFA. Advanced platelet-rich fibrin (A-PRF), absorbable collagen cone (ACC), venous blood, the combination of ACC and platelet-rich plasma (PRP), and the combination of ACC and enamel matrix derivative (EMD) were used in groups 2, 3, 4, 5, and 6, respectively. At the end of 4 and 12 weeks, three rabbits from each group were sacrificed by applying high-dose anesthetic, and samples were examined histologically and immunohistochemically. Results: Groups 2 and 5 showed significantly increased new bone formation compared with groups 1 and 4, 4 weeks after MSFA (P < .05). Twelve weeks after sinus floor augmentation, groups 2, 3, 5, and 6 showed significantly higher new bone formation than group 1 (P < .05). Groups 2 and 5 showed significantly higher hard tissue response than groups 1 and 4 at the end of 4 weeks (P < .05). Groups 5 and 6 demonstrated significantly higher hard tissue response than group 1 at the end of 12 weeks (P < .05). Group 5 also showed significantly higher hard tissue response than group 4 at the end of 12 weeks (P < .05). Immunohistochemical analysis showed a significant difference between the osteocalcin scores of groups 2 and 4 and group 1 at the end of 4 and 12 weeks (P < .05). There was also a statistically significant difference between osteocalcin scores at 4 and 12 weeks for groups 1 and 5 (P < .05). When osteopontin scores were compared, there was no significant difference between groups at 4 and 12 weeks (P > .05). Groups 1, 2, and 5 showed significant changes in osteopontin scores between 4 and 12 weeks (P < .05). Conclusion: The combination of ACC and PRP and the combination of ACC and EMD showed increased new bone formation and hard tissue response. A-PRF also showed promising results in new bone formation at the end of both 4 and 12 weeks. The usage of ACC as a carrier for liquid-form biomaterials may be more beneficial than the usage of ACC alone. [ABSTRACT FROM AUTHOR]

Background and Objectives: Enhanced osteoblast differentiation may be leveraged to prevent and treat bone-related diseases such as osteoporosis. No-ozone cold plasma (NCP) treatment is a promising and safe strategy to enhance osteoblast differentiation. Therefore, this study aimed to determine the effectiveness of direct and indirect NCP treatment methods on osteoblast differentiation. Mouse osteoblastic cells (MC3T3-E1) were treated with NCP using different methods, i.e., no NCP treatment (NT group; control), direct NCP treatment (DT group), direct NCP treatment followed by media replacement (MC group), and indirect treatment with NCP-treated media only (PAM group). Materials and Methods: The MC3T3-E1 cells were subsequently assessed for cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, and ALP and osteocalcin mRNA expression using real-time polymerase chain reaction. Results: Cell proliferation significantly increased in the NCP-treated groups (DT and PAM; MC and PAM) compared to the NT group after 24 h (p < 0.038) and 48 h (p < 0.000). ALP activity was increased in the DT and PAM groups at 1 week (p < 0.115) and in the DT, MC, and PAM groups at 2 weeks (p < 0.000) compared to the NT group. Calcium deposition was higher in the NCP-treated groups than in NT group at 2 and 3 weeks (p < 0.000). ALP mRNA expression peaked in the MC group at 2 weeks compared to the NP group (p < 0.014). Osteocalcin mRNA expression increased in the MC group at 2 weeks (p < 0.000) and was the highest in the PAM group at 3 weeks (p < 0.000). Thus, the effects of direct (DT and MC) and indirect (PAM) treatment varied, with MC direct treatment showing the most significant impact on osteoblast activity. Conclusions: The MC group exhibited enhanced osteoblast differentiation, indicating that direct NCP treatment followed by media replacement is the most effective method for promoting bone formation.

The aim of the present review is to discuss the roles of vitamin K (phylloquinone or menaquinones) and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for the maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated, these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. An adequate vitamin K status is required for the carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanisms, such as menaquinone 4 acting as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through the dietary adequacy of vitamin K. Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3, we find that an adequate supply of vitamin K, on top of an optimal vitamin D status, seems to add to the benefit of maintaining bone health. More research related to synergism and the possible mechanisms of vitamins D3 and K interaction in bone health is needed.

The purpose of the present study was to evaluate the concentrations of some bone turnover markers in preterm neonates with uncomplicated clinical course in the first month of life. Samples from 13 preterm neonates were collected at three different times: at birth (T0) from umbilical cord blood (UCB); and at 15 (T1) and 30 (T2) days of life from peripheral blood (PB). The concentrations of calcium (Ca), phosphate (P), total alkaline phosphatase (ALP), Collagen Type 1 Amino-terminal Propeptide (PINP), osteocalcin (OC), Collagen Type 1 Carboxyl-Terminal Telopeptide (CTX) and Leptin were assessed. A statistically significant difference for ALP concentration at birth versus T1 and T2 was found. An evident increase in the median concentrations of CTX, OC and PINP from T0 to T2 were observed. A significant difference was also found for Leptin concentration at T0 compared to T1. In preterm infants, in the absence of acute or chronic medical conditions and without risk factors for metabolic bone disease (MBD) of prematurity, there is a significant increase in bone turnover markers during the first month of life. The knowledge of the variations in these markers in the first weeks of life, integrated by the variations in the biochemical indicators of bone metabolism, could help in recognizing any conditions at risk of developing bone diseases.

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 Background The progressive deterioration of tissue–tissue crosstalk with aging causes a striking impairment of tissue homeostasis and functionality, particularly in the musculoskeletal system. Rejuvenation of the systemic and local milieu via interventions such as heterochronic parabiosis and exercise has been reported to improve musculoskeletal homeostasis in aged organisms. We have shown that Ginkgolide B (GB), a small molecule from Ginkgo biloba, improves bone homeostasis in aged mice by restoring local and systemic communication, implying a potential for maintaining skeletal muscle homeostasis and enhancing regeneration. In this study, we investigated the therapeutic efficacy of GB on skeletal muscle regeneration in aged mice. Methods Muscle injury models were established by barium chloride induction into the hind limb of 20‐month‐old mice (aged mice) and into C2C12‐derived myotubes. Therapeutic efficacy of daily administrated GB (12 mg/kg body weight) and osteocalcin (50 μg/kg body weight) on muscle regeneration was assessed by histochemical staining, gene expression, flow cytometry, ex vivo muscle function test and rotarod test. RNA sequencing was used to explore the mechanism of GB on muscle regeneration, with subsequent in vitro and in vivo experiments validating these findings. Results GB administration in aged mice improved muscle regeneration (muscle mass, P = 0.0374; myofiber number/field, P = 0.0001; centre nucleus, embryonic myosin heavy chain‐positive myofiber area, P = 0.0144), facilitated the recovery of muscle contractile properties (tetanic force, P = 0.0002; twitch force, P = 0.0005) and exercise performance (rotarod performance, P = 0.002), and reduced muscular fibrosis (collagen deposition, P

The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically healthy persons who needed teeth rehabilitation using dental implants. The conical-shaped implants (CI) and hexagonal implants (HI) were used. The content of Osteopontin (OPN), Osteocalcin (OC), Alkaline Phosphatase (ALP), Osteoprotegerin (OPG), and nitric oxide (NO) was determined in patients’ gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF), collected 1, 3, and 6 months after implantation. During the 3–6 months of observation level of OPN increased in patients with CIs ( 50 years) and HIs (50 years F = 30.104, p < 0.001; HI < 50 years F = 2.246, p < 0.001), ALP increased in patients with CIs (50 years: F = 12.01; p = 0.001) and HIs (50 years - on the 3 days month (CI: F = 18.82, p < 0.001; HI: F = 26.26, p < 0.001), but sharply decreased at the end of sixth month. OPG increased during 1–3 months of the observation in patients 50 years) during 1–6 months of the observation (F = 27.657, p < 0.001). During the post-implantation period, age-related differences in osteointegration were observed. Patients

ABSTRACT: Fatty liver hemorrhage syndrome (FLHS) is the leading cause of noninfectious mortality in caged layers worldwide. Osteocalcin (OCN) is a protein secreted by osteoblasts, and its undercarboxylated form (ucOCN) acts as a multifunctional hormone that protects laying hens from FLHS. Lipophagy is a form of selective autophagy that breaks down lipid droplets (LDs) through lysosomes, and defective lipophagy is associated with FLHS. The aim of this study was to investigate the effects of ucOCN on the lipophagy of chicken embryonic hepatocytes and associated the function of the adiponectin (ADPN) signaling pathway. In this study, chicken embryonic hepatocytes were divided into 5 groups: control (CONT), fat emulsion (FE, 10% FE, v/v), FE with ucOCN at 1 ng/mL (FE-LOCN), 3 ng/mL (FE-MOCN), and 9 ng/mL (FE-HOCN). In addition, 4 μM AdipoRon, an adiponectin receptor agonist, was used to investigate the function of ADPN. The results showed that compared with CONT group, FE promoted the levels of phosphorylation of mammalian target of rapamycin (p-mTOR) (P < 0.05) and decreased the mRNA expression of ADNP receptors (AdipoR1 and AdipoR2). Compared with FE group, 3 and 9 ng/mL ucOCN inhibited the levels of autophagy adaptor p62 and p-mTOR (P < 0.05), increased the ratios of LC3-II/LC3-I (P < 0.05) and phosphorylated adenosine 5′-monophosphate-activated protein kinase (p-AMPK)/AMPK (P < 0.05), as well as the levels of peroxisome proliferator-activated receptor α (PPAR-α) and ADPN (P < 0.05). In addition, ucOCN at the tested concentrations increased the colocalization of LC3 and LDs in fatty hepatocytes. Administrated 4 μM AdipoRon activated AdipoR1 and AidpoR2 mRNA expression (P < 0.05), decreased the concentrations of triglyceride (P < 0.05), without effects on cell viability (P > 0.05). AdipoRon also increased the LC3-II/LC3-I ratio (P < 0.05) and the levels of p-AMPK/AMPK and PPAR-α (P < 0.05). In conclusion, the results reveal that ucOCN regulates lipid metabolism by activating lipophagy via the ADPN-AMPK/PPARα-mTOR signaling pathway in chicken embryonic hepatocytes. The results may provide new insights for controlling FLHS in laying hens.

Three-dimensional (3D) cell culture systems provide more physiologically relevant information, representing more accurately the actual microenvironment where cells reside in tissues. However, the differences between the tissue culture plate (TCP) and 3D culture systems in terms of tumour cell growth, proliferation, migration, differentiation and response to the treatment have not been fully elucidated. Tumoroid microspheres containing the MDA-MB 231 breast cancer cell line were prepared using either tunable PEG-fibrinogen (PFs) or tunable PEG-silk fibroin (PSFs) hydrogels, respectively named MDAPFs and MDAPSFs. The cancer cells in the tumoroids showed changes both in globular morphology and at the protein expression level. A decrease of both Histone H3 acetylation and cyclin D1 expression in all 3D systems, compared to the 2D cell culture, was detected in parallel to changes of the matrix stiffness. The effects of a glutathionylated garlic extract (GSGa), a slow H2S-releasing donor, were investigated on both tumoroid systems. A pro-apoptotic effect of GSGa on tumour cell growth in 2D culture was observed as opposed to a pro-proliferative effect apparent in both MDAPFs and MDAPSFs. A dedicated ad hoc 3D cell migration chip was designed and optimized for studying tumour cell invasion in a gel-in-gel configuration. An anti-cell-invasion effect of the GSGa was observed in the 2D cell culture, whereas a pro-migratory effect in both MDAPFs and MDAPSFs was observed in the 3D cell migration chip assay. An increase of cyclin D1 expression after GSGa treatment was observed in agreement with an increase of the cell invasion index. Our results suggest that the “dimensionality” and the stiffness of the 3D cell culture milieu can change the response to both the gasotransmitter H2S and doxorubicin due to differences in both H2S diffusion and changes in protein expression. Moreover, we uncovered a direct relation between the cyclin D1 expression and the stiffness of the 3D cell culture milieu, suggesting the potential causal involvement of the cyclin D1 as a bio-marker for sensitivity of the tumour cells to their matrix stiffness. Therefore, our hydrogel-based tumoroids represent a valid tunable model for studying the physically induced transdifferentiation (PiT) of cancer cells and as a more reliable and predictive in vitro screening platform to investigate the effects of anti-tumour drugs.

Objective: To investigate the therapeutic efficacy of total flavonoids of Rhizoma Drynariae (TFRD) in conjunction with a calcium phosphate/collagen scaffold for the repair of cranial defects in rats. Methods: The subjects, rats, were segregated into four groups: Control, TFRD, Scaffold, and TFRD + Scaffold. Cranial critical bone defects, 5 mm in diameter, were artificially induced through precise drilling. Post-surgery, at intervals of 2, 4, and 8 weeks, micro-CT scans were conducted to evaluate the progress of skull repair. Hematoxylin–eosin and Masson staining techniques were applied to discern morphological disparities, and immunohistochemical staining was utilized to ascertain the expression levels of local osteogenic active factors, such as bone morphogenetic protein 2 (BMP-2) and osteocalcin (OCN). Results: Upon examination at the 8-week mark, cranial defects in the Scaffold and TFRD + Scaffold cohorts manifested significant repair, with the latter group displaying only negligible foramina. Micro-CT examination unveiled relative to its counterparts, and the TFRD + Scaffold groups exhibited marked bone regeneration at the 4- and 8-week intervals. Notably, the TFRD + Scaffold group exhibited substantial bone defect repair compared to the TFRD and Scaffold groups throughout the entire observation period, while histomorphological assessment demonstrated a significantly higher collagen fiber content than the other groups after 2 weeks. Immunohistochemical analysis further substantiated that the TFRD + Scaffold had augmented expression of BMP-2 at 2, 4 weeks and OCN at 2 weeks relative to other groups. Conclusions: The synergistic application of TFRD and calcium phosphate/collagen scaffold has been shown to enhance bone mineralization, bone plasticity, and bone histomorphology especially during initial osteogenesis phases. [ABSTRACT FROM AUTHOR]

Background: Due to the growing gap between the demand and supply of therapeutic services for people suffering from depression, with this study, we are investigating the effectiveness and factors of influence of new approaches in group treatments for depression. Two previous studies have already identified bouldering psychotherapy (BPT) as an effective option. It combines psychotherapeutic interventions with action- and body-oriented bouldering exercises. Mental model therapy (MMT) is a new cognitive-behavioral approach for treating depression. It focuses on identifying cognitive distortions, biases in decision making, and false assumptions and aims to correct and replace them with useful mental models. We aim to investigate the effectiveness of the interventions compared with a control group (CG) and to assess the factors of influence in a mixed methods approach. Methods: The study is being conducted as a randomized controlled intervention trial. Adult participants with unipolar depression are being randomized into three groups (BPT, MMT, or CG), and the first two groups are undergoing a 10-week treatment phase. CG follows their individual standard treatment as usual. A priori power analysis revealed that about 120 people should be included to capture a moderate effect. The primary outcome of the study is depression rated with the Montgomery and Asberg Depression Rating Scale (MADRS) before (t0), directly after (t1), and 12 months after the intervention phase (t2). Data are being collected via questionnaires, computer-assisted video interviews, and physical examinations. The primary hypotheses will be statistically analyzed by mixed model ANOVAs to compare the three groups over time. For secondary outcomes, further multivariate methods (e.g., mixed model ANOVAs and regression analyses) will be conducted. Qualitative data will be evaluated on the basis of the qualitative thematic analysis. Discussion: This study is investigating psychological and physical effects of BPT and MMT and its factors of influence on outpatients suffering from depression compared with a CG in a highly naturalistic design. The study could therefore provide insight into the modes of action of group therapy for depression and help to establish new short-term group treatments. Methodological limitations of the study might be the clinical heterogeneity of the sample and confounding effects due to simultaneous individual psychotherapy. Trial registration: ISRCTN, ISRCTN12347878. Registered 28 March 2022, https://www.isrctn.com/ISRCTN12347878. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic syndrome which is a syndrome complex that is associated with insulin resistance. Osteocalcin (OC), a bone derived protein has been found to decrease insulin resistance and stimulate production of insulin from the pancreas. Serum osteocalcin levels correlate with body mass index (BMI) and waist circumference. Thus, serum osteocalcin levels in metabolic syndrome could potentially be a new area to explore therapeutically. However, its role in clinical practice needs to be established. Methods: We conducted a cross-sectional study on patients, who visited Kasturba Hospital, Manipal between September 2018 and September 2020, to study the relationship between Serum Osteocalcin and the parameters of metabolic syndrome. All patients above the age of 18 years who satisfied the NCEP-ATP III guidelines (Asian adaptation) for metabolic syndrome were considered for the study. Patients who had thyroid and parathyroid disorders, bone malignancies, osteoporosis, liver failure and renal dysfunction were excluded. Results: A total of 115 subjects were analyzed. As serum osteoclacin increased, there was a significant decrease in fasting blood glucose levels (r = −.748, P <.05) and a significant increase in serum HDL levels (r =.617, P <.01). There was no correlation found between serum osteocalcin and BMI/waist circumference in this study. Finally, it was observed that individuals with fewer components of metabolic syndrome had a significantly higher serum osteocalcin when compared with individuals with a higher number of components of metabolic syndrome (P <.01). Conclusion: This data further confirmed the association between serum OC and parameters of metabolic syndrome such as FBS and serum HDL. It also found that increased serum OC was associated with fewer components of the metabolic syndrome indicating that OC could have a positive metabolic impact and may prevent atherosclerotic risk. [ABSTRACT FROM AUTHOR]

Secondary osteoporosis is mainly caused by prolong used of glucocorticoid treatment. The Piper sarmentosum leaf aqueous extract was found to exhibit bone formatting osteocalcin activity against Dexamethasone induced osteoporotic rats. Thirty-two Sprague-Dawley rats were divided equally into four groups - G1: Sham-operated control group given intramuscular (IM) olive oil as vehicle and normal saline orally as vehicle; G2: Adrenalectomized (Adrx) control group given IM dexamethasone (DEX) (120 μg/kg/day) and normal saline orally as vehicle; G3: Adrx group given IM DEX (120 μg/kg/day) and aqueous extract of Piper sarmentosum leaves (125 mg/kg/day) orally; and G4: Adrx group given IM DEX (120 μg/kg/day) and glycyrrhizic acid (GCA) (120 mg/kg/day) orally. Immunohistochemical method with gold labelling was used to label the osteocalcin protein. Silver brightener was used, sprinkled on gold with a size of 5 nm so that the resulting image can be seen more clearly using a light microscope. The osteocalcin protein was measured quantitatively based on nomenclature report of the ASBMR Histomorphometry Committee (American Society for Bone Mineral Research). The activity shown by immunohisto-gold expression and localization of osteocalcin was comparable with the reference, glycyrrhizic acid, a potent inhibitor of 11β-hydroxysteroid dehydrogenase enzyme in RANKL-OPG pathway. As a conclusion, Piper sarmentosum may one day be utilized as an alternate treatment for individuals receiving long-term glucocorticoid therapy to prevent osteoporosis, therefore osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Objectives: Osteoporosis (OP) is a usual disease with a possible genetic predisposition. IL-23 plays a role in physiological bone remodeling and regulates the activity of cells of the bone either directly or indirectly on bone-resorbing osteoclasts as well as on bone-forming osteoblasts. Recent animal and human trials have revealed the main pro-osteoclastogenic activities for the IL-23 pathway. We examined nine single nucleotide polymorphisms (SNPs) in the interleukin-23 receptor (IL-23R) in 100 OP patients and gender- and age-matched 96 healthy volunteers. The most analyzed SNPs in the recent rheumatology literature were selected. Methods: In addition to gene polymorphisms several laboratory parameters (osteocalcin, parathormone, vitamine D) were investigated. Independent Samples t-test and Mann-Whitney-U test were used to compare several demographic and clinical parameters between the groups. P - value < 0.05 was accepted to be statistically significant. Results: Having the heterozygous GA genotype of IL-23R rs1004819 and the heterozygous CT genotype of Il-23R rs7530511 significantly increase the risk of developing OP (adjusted OR: 3.51, p = 0.031 and OR: 2.41, p = 0.027, respectively). The wild homozygous GG genotype of Il-23R rs11209032 had higher osteocalcin levels compared with the mutant homozygous AA genotype (18.75 ± 9.76, p = 0.009). Conclusions: Our findings suggest that several IL-23R gene polymorphisms are seen more often in osteoporosis patients than in healthy volunteers. In addition, some SNPs were related to higher serum osteocalcin levels. [ABSTRACT FROM AUTHOR]

The amino acids arginine (Arg), asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are related to nitric oxide (NO) metabolism and potential markers of two different disease entities: cardiovascular disease such as atherosclerosis and systemic inflammation in critically ill patients with sepsis. Although very different in their pathophysiological genesis, both entities involve the functional integrity of blood vessels. In this context, large population-based data associating NO metabolites with proinflammatory markers, e.g., white blood cell count (WBC), high-sensitivity C-reactive protein (hsCRP), and fibrinogen, or cytokines are sparse. We investigated the association of Arg, ADMA and SDMA with WBC, hsCRP, and fibrinogen in 3556 participants of the Study of Health in Pomerania (SHIP)-TREND study. Furthermore, in a subcohort of 456 subjects, 31 inflammatory markers and cytokines were analyzed. We identified Arg and SDMA to be positively associated with hsCRP (β coefficient 0.010, standard error (SE) 0.002 and 0.298, 0.137, respectively) as well as fibrinogen (β 5.23 × 10−3, SE 4.75 × 10−4 and 0.083, 0.031, respectively). ADMA was not associated with WBC, hsCRP, or fibrinogen. Furthermore, in the subcohort, Arg was inversely related to a proliferation-inducing ligand (APRIL). SDMA was positively associated with osteocalcin, tumor necrosis factor receptor 1 and 2, and soluble cluster of differentiation 30. Our findings provide new insights into the involvement of Arg, ADMA, and SDMA in subclinical inflammation in the general population. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer's disease (AD). Extracellular aggregates of amyloid-β (Aβ) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in the AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated Aβ and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on the mechanisms behind exercise-induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer's disease pathology. Exercise releases into the circulation a host of hormones and factors from a variety of peripheral tissues. Mechanisms of BDNF induction discussed here are osteocalcin, FNDC5/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are not yet fully understood but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline. [ABSTRACT FROM AUTHOR]

In this study we aimed at analysing the effects of different weekly exercise volumes (1, 2 or 3 times 60-min) on bone health, body composition and physical fitness of inactive middle-to-older-aged males, after 16 weeks of recreational team handball (RTH). Fifty-four men (68 ± 4 years, stature 169 ± 6 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups (TH1, n = 13; TH2, n = 15; or TH3, n = 12, performing 1, 2 and 3 weekly 60-min training sessions, respectively), and a control group (CG, n = 14). The training sessions consisted mainly of RTH matches played as small-sided and formal game formats (4v4, 5v5, 6v6 or 7v7) with adapted rules. Matches' mean and peak heart rate (HR) ranged from 78–80% and 86–89%HRmax, respectively, and distance covered from 4676 to 5202 m. A time x group interaction was observed for procollagen type-1 amino-terminal propeptide (P1NP), osteocalcin (OC), carboxy-terminal type-1 collagen crosslinks (CTX), sclerostin, upper and lower body dynamic strength, right arm fat mass, left and right arm, right leg and android total mass (TM; p ≤ 0.047) with the greatest effects being shown for TH2 and TH3 groups. Post-intervention group differences were observed in CTX, left arm and right leg TM (TH3 > TH1), P1NP (TH2 > CG), OC, right arm TM (TH3 > CG), upper (CG < TH1, TH2 and TH3) and lower body dynamic strength (CG < TH1 and TH3) (p ≤ 0.047). RTH was effective in enhancing bone health, body composition and physical fitness in middle-to-older-aged males, especially for the intervention groups that performed 2–3 weekly training sessions. ClinicalTrials.gov ID: NCT05295511. Trial registration: ClinicalTrials.gov identifier: NCT05295511. Highlights After 16 weeks of recreational team handball small-sided and formal matches, inactive middle-to-older-aged males improved bone health, body composition and physical fitness, by performing 1, 2 or 3 60-min weekly sessions, however, greater improvements were shown in the groups that performed 2 or 3 weekly training sessions. Training intensity was similar across the intervention groups that performed recreational team handball for 1, 2 or 3 60-min weekly sessions, which means that training volume is most likely to be the reason for the different health effects shown. The very high fun levels reported by all intervention groups shows that recreational team handball is a social and fun exercise modality for middle-to-older-aged males, with potential to intrinsically motivate the participants and assure long-term adherence to exercise. [ABSTRACT FROM AUTHOR]

Bone fracture healing is a complex biological process involving four phases coordinated over time: hematoma formation, granulation tissue formation, bony callus formation, and bone remodelling. Bone fractures represent a significant health problem, particularly among the elderly population and patients with comorbidities. Therapeutic strategies proposed to treat such fractures include the use of autografts, allografts, and tissue engineering strategies. It has been shown that bone morphogenetic protein 2 (BMP-2) has a therapeutic potential to enhance fracture healing. Despite the clinical efficacy of BMP-2 in osteoinduction and bone repair, adverse side effects and complications have been reported. Therefore, in this in vitro study, we propose the use of a disaccharide compound (DP2) to improve the mineralisation process. We first evaluated the effect of DP2 on primary human osteoblasts (HOb), and then investigated the mechanisms involved. Our findings showed that (i) DP2 improved osteoblast differentiation by inducing alkaline phosphatase activity, osteopontin, and osteocalcin expression; (ii) DP2 induced earlier in vitro mineralisation in HOb cells compared to BMP-2 mainly by earlier activation of Runx2; and (iii) DP2 is internalized in HOb cells and activates the protein kinase C signalling pathway. Consequently, DP2 is a potential therapeutical candidate molecule for bone fracture repair. [ABSTRACT FROM AUTHOR]

Purpose: There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. Methods: The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. Results: Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. Conclusion: Our findings do not support the claim that proteins of dairy origin are detrimental to bone health. [ABSTRACT FROM AUTHOR]

Objective: Special AT‐rich binding protein 1 (SATB1), a chromatin organizer and global transcriptional regulator, plays an important role in tumorigenesis and immune response. However, its function in the osteogenic differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) remains unknown. Therefore, this study aimed to explore the role of SATB1 in osteogenesis. Methods: BMSCs were collected from the type 2 diabetes rat model and the protein and gene expression of SATB1 and osteospecific genes were evaluated post osteogenic induction. Results: SATB1 protein expression significantly decreased in diabetic rat BMSCs whereas it increased in BMSCs following osteogenic induction. SATB1 knockdown significantly suppressed the expression of osteospecific genes, including alkaline phosphatase (Alp), runt‐related transcription factor 2, and osteocalcin, and reduced the number of mineral deposits and ALP activity, whereas SATB1 overexpression yielded the opposite results. Moreover, SATB1 knockdown suppressed activation of the MAPK signalling pathway (phosphorylation of p38 and ERK), and MAPK pathway inhibitors could reverse the inhibitory effect of SATB1 knockdown on osteogenic differentiation of BMSCs. Conclusion: SATB1 plays a key role in the osteogenic differentiation of BMSCs via the p38 MAPK and ERK MAPK signalling pathways. These findings may provide a new strategy for the application of BMSCs in bone regeneration. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a potent antiviral, anti-inflammatory, and antibacterial agent found in cow and human colostrum which acts as an osteogenic growth factor. This study aimed to investigate whether LF-anchored tannylated mesoporous silica nanomaterials (TA-MSN-LF) function as a bone fusion material in a rat model. In this study, we created TA-MSN-LF and measured the effects of low (1 μg) and high (100 μg) TA-MSN-LF concentrations in a spinal fusion animal model. Rats were assigned to four groups in this study: defect, MSN, TA-MSN-LF-low (1 μg/mL), and TA-MSN-LF-high (100 μg/mL). Eight weeks after surgery, a greater amount of radiological fusion was identified in the TA-MSN-LF groups than in the other groups. Hematoxylin and eosin staining showed that new bone fusion was induced in the TA-MSN-LF groups. Additionally, osteocalcin, a marker of bone formation, was detected by immunohistochemistry, and its intensity was induced in the TA-MSN-LF groups. The formation of new vessels was induced in the TA-MSN-LF-high group. We also confirmed an increase in the serum osteocalcin level and the mRNA expression of osteocalcin and osteopontin in the TA-MSN-LF groups. TA-MSN-LF showed effective bone fusion and angiogenesis in rats. We suggest that TA-MSN-LF is a potent material for spinal bone fusion. [ABSTRACT FROM AUTHOR]

Triggered by the association of malnutrition with the incidence of fractures in patients undergoing hemodialysis (HD), the present study evaluated whether the body mass index (BMI) is associated with serum markers of osteoblastic or osteoclastic activity in this population. The levels of the osteoblastic markers, total procollagen type-1 aminoterminal propeptide (P1NP) and osteocalcin (OC), the osteoclastic marker, ß-isomerized C-terminal cross-linked peptide of collagen type I (ß-CTx), and those of the intact parathyroid hormone (iPTH) were measured in the serum of 59 patients undergoing HD. iPTH, P1NP, OC and ß-CTx were intercorre-lated. BMI inversely correlated with the osteoblastic markers, P1NP and OC, but not with the osteoclastic marker, ß-CTx. Age negatively correlated with OC, ß-CTx and iPTH. The levels of P1NP, OC and ß-CTx were lower in patients with diabetes mellitus. BMI affected the osteoblastic markers independently of age, diabetes mellitus and iPTH. Thus, BMI inversely correlates with markers of osteoblastic activity in patients undergoing HD. However, other studies are required to confirm causality in this correlation. If confirmed, then enhancing osteoblastic activity by improving the nutritional status may become another therapeutic strategy against chronic kidney disease-mineral bone disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression changes and clinical significance of serum N-terminus of type Ⅰ collagen (NTx), C-terminus of type Ⅰ collagen (CTX), and osteocalcin (BGP) in postmenopausal osteoporosis patients. Methods: Sixty postmenopausal osteoporosis patients admitted to our hospital from August 2017 to August 2022 were selected as the study subjects and divided into the observation group, and another 60 postmenopausal healthy volunteers who came to our hospital for physical examination during the same period were selected as the control group. The expression levels of NTx, CTX and BGP were compared between the two groups, and subject work characteristic (ROC) curves were established to analyze the diagnostic efficacy of NTx, CTX and BGP on postmenopausal osteoporosis. 35 postmenopausal osteoporosis patients with obvious and significant symptom reduction, significant improvement in X-ray examination and significant increase in BMD values were divided into the good prognosis group, and the remaining 25patients who did not meet the above criteria were divided into the poor prognosis group. The clinical general conditions of the two groups were compared, and logistic regression was applied to analyze the prognostic predictive value of NTx, CTX and BGP on postmenopausal osteoporosis. Results: The comparison of NTx, CTX and BGP expression levels between the two groups of subjects was significantly different, with NTx and CTX higher in the observation group and BGP lower in the control group (P＜0.05) ; the diagnostic efficacy of the combination of NTx, CTX and BGP for postmenopausal osteoporosis was better than that of a single test (P＜0.05) ; the comparison of age,BMI, combined underlying disease, and Ca expression levels between the good prognosis group and the poor prognosis group was not significantly different (P＞0.05), There was no significant difference between the good prognosis group and the poor prognosis group in terms of age, BMI, combined underlying disease, disease duration, Ca expression level (P＞0.05), and significant difference between the good prognosis group and the poor prognosis group in terms of severity of disease, BMD T value, estradiol, serum NTx, CTX, BGP expression level (P＜0.05) ; logistic regression analysis showed that CTX and BGP were independent influences on poor prognosis of postmenopausal osteoporosis factors (P＜0.05) . Conclusion: The expression levels of type I collagen amino terminal and type Ⅰ collagen carboxyl terminal in serum of postmenopausal osteoporosis patients are higher than those of non osteoporosis groups, and osteocalcin is lower than that of non osteoporosis groups. The combination of the three can improve the diagnostic efficacy of postmenopausal osteoporosis.In addition, CTX and BGP are independent influencing factors for poor prognosis of postmenopausal osteoporosis. Higher levels of CTX and lower levels of BGP may indicate poor prognosis in patients. Therefore, timely improvement of treatment measures is necessary in clinical practice to improve the prognosis of such patients. [ABSTRACT FROM AUTHOR]

Male reproductive functions and bone health are both adversely affected by the high salt diet (HSD). Nevertheless, the underlying mechanism via which it alters the sperm function remains largely unknown. This study examines the mechanism by which HSD affects male fertility by impairing bone health. For investigating the same, male BALB/c mice were categorized into three groups—HSD group (fed with 4% NaCl), a low salt diet (LSD) group (fed with 0.4% NaCl), and a control group (fed with a normal diet) for 6 weeks and thereafter assessed for various sperm parameters, bone turnover markers, and testosterone levels. Furthermore, the quantitative assessment of testosterone biosynthesis enzymes was performed. Interestingly, we observed that mice fed with HSD showed significant alterations in sperm parameters—motility, count, and vitality, including morphological changes compared to both the LSD and the control groups. In addition, serum analysis showed an increase in bone resorption markers and a decrease in bone formation markers in the HSD group (p < 0.05). Further, HSD caused a decrease in the testosterone level and mRNA expression of testosterone biosynthesis enzymes. Importantly, a significant decrease in bone formation marker osteocalcin (OC) was observed to coincide with the dip in testosterone level in the HSD group. Given that OC plays a key role in maintaining male fertility, the above findings suggest that a decrease in OC levels may affect the testosterone biosynthesis pathway, reducing testosterone hormone secretion and thereby resulting in decreased spermatogenesis. The study for the first time delineates and bridges the mechanism of HSD-mediated bone loss (results in a deficiency of OC) with decreased testosterone biosynthesis and thus impaired male fertility. [ABSTRACT FROM AUTHOR]

To explore beta-sitosterol involved in regulating the mechanism of postmenopausal osteoporosis in the elderly through the phosphoinositide-3-kinase--protein kinase B. 90 Sprague Dawley grade female rats were selected as the research subjects and randomly divided into a control, beta-sitosterol treatment, and the model group. Establishing an elderly postmenopausal osteoporosis model using oophorectomy, beta-sitosterol treatment group was given 20 μmol/l, the model group and control group were given equal volume of 0.9 % physiological saline by gavage of sitosterol drugs. In terms of bone mineral density, the bone mineral density in the beta-sitosterol group was raised than that in the model group. The results of hematoxylin and eosin staining showed that the degree of osteoporosis in the beta-sitosterol group was less than that in the model group. Enzyme-linked immunosorbent assay results showed that the concentrations of serum estradiol, bone alkaline phosphatase, osteocalcin and procollagen N-terminal propeptide in the beta-sitosterol group were raised than those in the model group. Quantitative polymerase chain reaction results showed that the expression of phosphoinositide-3-kinase--protein kinase B messenger ribonucleic acid in bone tissue of beta-sitosterol treated group was raised than that of model group. Western blot analysis showed that the expression of phosphoinositide-3-kinase--protein kinase B was increased in beta-sitosterol treated group. Further experiments confirmed that the protective effect of beta-sitosterol on senile postmenopausal osteoporosis could be reversed by inhibiting phosphoinositide-3-kinase--protein kinase B. Beta-sitosterol can regulate senile postmenopausal osteoporosis and regulate the expression of bone mineral density and osteogenesis-related factors through phosphoinositide-3-kinase--protein kinase B signal pathway. [ABSTRACT FROM AUTHOR]

Osteoporosis has gradually become a common human disease. The main cause of this common disease is caused by the degradation of the internal structure of bone and soft tissues, which causes great troubles to the lives of elderly patients. Quercetin is a flavonoid drug that is commonly used to treat osteoporosis. Therefore, it is very important to study the pharmacological and clinical effects of quercetin. The purpose of this article is to solve some problems in the clinical application of quercetin and to explore the effect of quercetin on bone metabolism and serum osteocalcin in osteoporotic rats. Taking 90 rats as the research object, an animal model of osteoporosis was constructed. The rats were randomly divided into sham operation control group, ovariectomy control group and quercetin observation group. Except for the sham operation group, all rats were subjected to ovariectomy, and the rats in the quercetin observation group were given quercetin drug intervention. 1 w later, all rats were tested for bone metabolism and serum osteocalcin levels, and related data were recorded and analyzed. The results of the study showed that with the intervention of quercetin, the bone metabolism index of osteoporosis rats increased from the original (53.49±3.41) to (86.27.2±4.22), and the serum calcium level from the original (16.28±0.56) μg/l increased to (37.64±2.35) μg/l, and the bone mineral density and bone tissue structure of rats also improved accordingly. It can be seen that quercetin can promote bone metabolism in osteoporotic rats, increase the content of osteocalcin in rats, and have a good effect on the prevention and treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Exercise is beneficial to bone health. However, little is known about the interaction effect of gender and sport type on bone turnover in young athletes. This study aimed to examine the influence of gender and sports categories (high, medium, and low impact) on bone turnover: reabsorption markers–osteocalcin, calcium, inorganic phosphate (IP), alkaline phosphatase (ALP), and resorption marker–cross-linked N-telopeptides of type 1 collagen (NTx) among a university's undergraduate athletes. Methods: The study was an ex-post facto design involving forty-seven purposively recruited gender- and sport-type-matched undergraduate athletes whose demographic characteristics and BMI were obtained. Participants' 5 mL antecubital blood samples were collected and analysed for serum levels of osteocalcin, calcium, IP, ALP, and NTx using standard laboratory protocols, Bio-Tek spectrometer, and KC4 (3.3) software. Data were analysed using descriptive statistics and two-way ANOVA. Results: The study involved 24 females and 23 males (n = 47) aged 22.15 ± 3.35 years with an average BMI of 23.34 ± 4.66. There was no significant gender effect on the biomarkers. However, there was a significant effect of the sports category on IP (F = 4.307, p = 0.020), calcium (F = 6.807, p = 0.003), and ALP serum levels (F = 11.511, p < 0.001). Specifically, mid-impact sports participants had a higher IP than the low-impact group (mean difference [MD] = 0.81 mg/dL, p = 0.036). Low-impact had a higher calcium level than mid-impact (MD = 0.40 mg/dL, p = 0.022) and high-impact (MD = 0.49 mg/dL, p = 0.003). Conversely, low-impact had lower ALP than mid-impact (MD = − 11.13 U/L, p = 0.013) and high-impact (MD = − 17.44 IU/L, p < 0.001). Conclusion: Moderate to high-impact sports positively affected bone turnover in young athletes. However, gender had no significant impact. [ABSTRACT FROM AUTHOR]

Aim: The effects of vitamin D administration on bone turnover markers (BTMs) in adults are controversial. Thus, we carried out a meta‐analysis of available randomised controlled trials (RCTs) to examine the impact of vitamin D supplementation on BTMs. Methods: To identify relevant RCTs, we searched the PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library and Embase databases for manuscripts published up to July 2022. The present study was conducted in agreement with the PRISMA guidelines. Weighed mean difference (WMD) and 95% confidence intervals (CI) were used to calculate the magnitude of the effect of the intervention. Results: A total of 42 RCTs were included in the meta‐analysis. The age of the participants enrolled in the RCTs ranged from 19.4 to 84 years. The pooled results depicted a decrease in deoxypyridinoline (DPD) concentrations (WMD: −1.58 nmol/mmol, 95% CI: −2.55, −.61, p =.001) following vitamin D supplementation. In addition, subgroup analyses demonstrated that vitamin D administration notably reduced procollagen type I N‐terminal propeptide (PINP) levels in individuals aged >50 years and led to a pronounced decrease in alkaline phosphatase (ALP) values when the intervention lasted >12 weeks. No significant effect was observed on other BTMs, for example, collagen type 1 cross‐linked C‐telopeptide (CTX) and osteocalcin (OC) levels. Conclusion: Vitamin D administration decreases DPD, PINP and ALP levels, indicating a reduced bone turnover following the intervention. Other BTMs, for example, CTX or OC values, were not affected by vitamin D prescription. Vitamin D supplementation may exert a positive effect on some important BTMs. [ABSTRACT FROM AUTHOR]

Kefir is a natural source of probiotics, and yacon (Smallanthus sonchifolius) is a tuberous root rich in fructooligosaccharides, with prebiotic properties. We hypothesized that kefir and yacon can improve bone and intestinal health and that their synbiotic effects will enhance these benefits. The properties of yacon and kefir and their association were evaluated in the intestinal and bone health in rats. Forty Wistar male rats were divided into 4 groups (n = 10): control (C), kefir (K), yacon (Y), and yacon + kefir (YK) and received an AIN-93 M diet containing 50% of the daily recommendation of calcium for 42 days. Group K received 1 mL/day of kefir containing 10⁸ CFU/mL; group Y received yacon flour (5% fructooligosaccharides); and the YK group received the same treatment as the Y and K groups. Urine and feces were collected to determine the calcium balance. Serum biomarkers of bone formation and resorption, osteocalcin, N telopeptides of collagen type I and C-telopeptide of collagen type I, intraluminal pH, intestinal permeability, and secretory immunoglobulin A were evaluated. Yacon reduced intraluminal pH alone or in association with kefir (groups Y and YK). Yacon also improved intestinal permeability (lowered lactulose and mannitol excretion) and increased calcium balance and osteocalcin, a biomarker of bone formation. In turn, K improved immunity by increasing secretory immunoglobulin A secretion and reducing bone resorption biomarkers (C-telopeptide of collagen type I and N telopeptides of collagen type I). Thus, yacon and kefir had beneficial effects on intestinal and bone health; however, the association between them did not demonstrate a synbiotic effect. Kefir is a natural source of probiotics, and yacon is rich in fructooligosaccharides, with prebiotic properties. The consumption of kefir and yacon alone or in combination can promote bone and intestinal health benefits. Wistar male rats were divided into 4 groups: control, kefir, yacon, and yacon + kefir. Yacon reduced pH, improved intestinal permeability, and increased calcium balance and a biomarker of bone formation. Kefir increased secretory immunoglobulin A secretion and reduced bone resorption biomarkers. Yacon + kefir reduced pH. Thus, yacon and kefir had beneficial effects on intestinal and bone health. However, the association between them did not demonstrate a symbiotic effect. [Display omitted] [ABSTRACT FROM AUTHOR]