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Recently, interest in fish byproduct-derived bioactive components as potential ingredients for treating and preventing osteoporosis is increasing. In this study, we investigated the antiosteoporotic effects of mackerel Scomber japonicus extracts in MC3T3-E1 preosteoblasts in vitro and ovariectomized rats in vivo. Scomber japonicus neutrase-assisted protein hydrolysate (SJNH) treatment enhanced alkaline phosphatase (ALP) activity and osteoprotegerin (OPG) level, and attenuated receptor activator of nuclear factor κB ligand (RANKL) level in MC3T3-E1 cells. In an osteoporotic animal model, ovariectomized (OVX) rats were administered SJNH (200 mg/kg/day) for 8 weeks. SJNH prevented OVX-induced bone mineral density (BMD) loss and restored bone structural compartment loss based on micro-computed tomography (CT). In addition, SJNH administration normalized bone remodeling by regulating bone regeneration and resorption-related proteins such as ALP, osteocalcin (OC), and tartrate-resistant acid phosphatase 5b (TRACP-5b) as well as calcium contents in serum. Taken together, our findings suggest that SJNH can promote antiosteoporotic effects both in vitro and in vivo. Thus, SJNH might be a potent therapeutic agent or functional food ingredient for preventing osteoporosis. [ABSTRACT FROM AUTHOR]

Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis. [ABSTRACT FROM AUTHOR]

The ethanol extract of Persea americana seeds was found to inhibit the development of estrogen-dependent conditions in female Wistar rats, suggesting the ability of its secondary metabolites to interact with estrogen receptors (ERs), either as partial agonists or as antagonists. To test this hypothesis, the abovementioned extract was assessed for its ability to mimic and/or antagonize estradiol effects. Two experiments were conducted in ovariectomized (OVX) rats: (1) animals were treated with estradiol valerate (E2V; 1 mg/kg) or P. americana at doses of 25 and 50 mg/kg; (2) animals were treated with E2V alone (0.75 mg/kg) or in combination with P. americana at the abovementioned doses. Treatments were given orally for 3 days and animals were sacrificed for biochemical and histological analyses of the uterus and vagina. When administered alone, P. americana did not change the histomorphology of both organs (uterus and vagina). In combination with E2V, P. americana decreased uterine weight [30 % decrease (p<0.001) at 25 mg/kg and 24 % (p<0.01) at 50 mg/kg] and epithelium height (37 % decrease). This was associated with decreased estradiol levels (at least 86 % decrease, p<0.001) in the uterus. Similarly, vagina epithelium height decreased by at least 34 % (p<0.05) when E2V was co-administered with P. americana. The seed extract of P. americana contains ER antagonist secondary metabolites accounting for its ability to inhibit the development of estrogen-dependent conditions in female rats. [ABSTRACT FROM AUTHOR]

Abstract Background Bone is continuously produced by osteoblasts and resorbed by osteoclasts to maintain homeostasis. Impaired bone resorption by osteoclasts causes bone diseases such as osteoporosis and arthritis. Most pharmacological treatment of osteoporosis focuses on inhibiting osteoclast differentiation, often to restore osteoclast/osteoclast balance. However, recent osteoporosis treatments have various side effects. According to a recent study, resveratrol, known as a stilbenoid family, is known to increase bone density, and the osteoclast inhibitory effect was confirmed using oxyresveratrol, a stilbenoid family. Here, we investigated the effect of oxyresveratrol on osteoclast differentiation and an ovariectomized mouse model. Methods Mouse leukemia monocyte/macrophage cell line RAW 264.7 was treated with oxyresveratrol, and cell cytotoxicity was confirmed by measuring MTT assay. Tartrate-resistant acid phosphatase (TRAP), an enzyme marker for osteoclasts, was confirmed by staining. In addition, osteoclast differentiation markers and MAPK-related markers were confirmed at the mRNA level and protein expression. The effect of oxyresveratrol was confirmed using ovariectomized mice. Deoxypyridinoline (DPD) was measured using mouse urine and TRAP activity was observed using serum. Bone mineral density was also measured using Micro-CT. Results The polyphenol oxyresveratrol inhibited receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells. Furthermore, oxyresveratrol inhibited TRAP activity and actin-ring formation. Moreover, oxyresveratrol suppressed the phosphorylation of the RANKL-induced mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK and significantly reduced the expression of bone differentiation markers (NFATc1, cathepsin K, and TRAP). Conclusion Oxyresveratrol inhibits osteoclast differentiation via MAPK and increases bone density in ovariectomized rats, suggesting it has therapeutic potential for bone diseases such as osteoporosis. We confirmed the osteoporosis prevention effect of OR in Raw 264.7 cells, and future studies should confirm the effect of OR using rat bone marrow-derived cells.

Background: Bone is continuously produced by osteoblasts and resorbed by osteoclasts to maintain homeostasis. Impaired bone resorption by osteoclasts causes bone diseases such as osteoporosis and arthritis. Most pharmacological treatment of osteoporosis focuses on inhibiting osteoclast differentiation, often to restore osteoclast/osteoclast balance. However, recent osteoporosis treatments have various side effects. According to a recent study, resveratrol, known as a stilbenoid family, is known to increase bone density, and the osteoclast inhibitory effect was confirmed using oxyresveratrol, a stilbenoid family. Here, we investigated the effect of oxyresveratrol on osteoclast differentiation and an ovariectomized mouse model. Methods: Mouse leukemia monocyte/macrophage cell line RAW 264.7 was treated with oxyresveratrol, and cell cytotoxicity was confirmed by measuring MTT assay. Tartrate-resistant acid phosphatase (TRAP), an enzyme marker for osteoclasts, was confirmed by staining. In addition, osteoclast differentiation markers and MAPK-related markers were confirmed at the mRNA level and protein expression. The effect of oxyresveratrol was confirmed using ovariectomized mice. Deoxypyridinoline (DPD) was measured using mouse urine and TRAP activity was observed using serum. Bone mineral density was also measured using Micro-CT. Results: The polyphenol oxyresveratrol inhibited receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells. Furthermore, oxyresveratrol inhibited TRAP activity and actin-ring formation. Moreover, oxyresveratrol suppressed the phosphorylation of the RANKL-induced mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK and significantly reduced the expression of bone differentiation markers (NFATc1, cathepsin K, and TRAP). Conclusion: Oxyresveratrol inhibits osteoclast differentiation via MAPK and increases bone density in ovariectomized rats, suggesting it has therapeutic potential for bone diseases such as osteoporosis. We confirmed the osteoporosis prevention effect of OR in Raw 264.7 cells, and future studies should confirm the effect of OR using rat bone marrow-derived cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: Zoledronic acid mainly acts on the formation of osteoclasts and also inhibits osteoblast apoptosis, proliferation, and differentiation. However, the effect and mechanism of zoledronic acid on alveolar bone formation in ovariectomized rats are still controversial. OBJECTIVE: To explore the osteogenic effect of zoledronic acid on alveolar bone of ovariectomized rats via alveolar nucleotide-binding oligomerization domainlike receptor protein 3 (NLRP3)/cysteinyl-aspartate protease-1 (Caspase-1)/interleukin-1β pathway. METHODS: Totally 36 female Sprague-Dawley rats were randomly divided into control group, model group, and zoledronic acid group, with 12 rats in each group. Bilateral oophorectomy was used to establish an animal model of osteoporosis in the latter two groups. The zoledronic acid group was subcutaneously given 20 μg/kg zoledronic acid at 12 weeks after modeling, while the control and model groups were injected with the same dose of normal saline. All animals were anesthetized after 4-week drug intervention to collect serum samples from the abdominal aorta and alveolar bone samples. Serum alkaline phosphatase, osteocalcin and interleukin-1β levels were detected by ELISA. Hematoxylin-eosin staining was used to observe the pathological changes of rat alveolar bone. TUNEL staining was used to detect the apoptosis of osteoblasts in rat alveolar bone. The formation of alveolar bone was detected by calcein fluorescent labeling. Western blot assay was used to detect the levels of NLPR3, Caspase-1 and interleukin-1β in alveolar bone tissue as well the protein expression of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin. RESULTS AND CONCLUSION: Compared with the model group, the expression level of alkaline phosphatase in rat serum decreased in the zoledronic acid group (P < 0.01), while the expression level of osteocalcin increased significantly (P < 0.05). Compared with the model group, the pathological structure of alveolar bone in the zoledronic acid group was improved. The number of TUNEL positive cells in the zoledronic acid group was significantly lower than that in the model group (P < 0.001). The mineralization deposition rate and new bone formation rate of trabecular bone in the zoledronic acid group were higher than those in the model group (P < 0.05). (5) Western blot results showed that compared with the control group, NLRP3, Caspase-1, interleukin-1β proteins was highly expressed in the model group (P < 0.05), while the expressions of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin proteins were decreased (P < 0.05). However, treatment with zoledronic acid decreased the protein expression of NLRP3, Caspase-1, and interleukin-1β (P < 0.05), but increased the protein expression of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin (P < 0.05). The above results show that zoledronic acid can affect the expression of osteogenic related factors and inflammatory factors in serum to improve bone metabolism and inflammatory response, enhance the differentiation function of osteoblasts, and delay the formation of osteoporosis. Zoledronic acid can improve alveolar bone structure, reduce alveolar bone osteoblast apoptosis and the protein expression of NLRP3, Caspase-1, and interleukin-1β, increase the mineralization deposition rate and new bone formation rate of alveolar bone trabecula and the protein expression of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin, which may be related to the inhibition of NLRP3/Caspase-1/interleukin-1β signaling pathway. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis (PMOP) is a chronic bone metabolic disease, which often causes fractures and various complications, it causes a great social and economic burden, and it is urgent to use modern research techniques to elucidate the pathogenesis of PMOP. At the same time, because of the complex physiological and pathological interaction mechanism between osteoporosis and sarcopenia, the correlation research has become a hot topic. Ovary removal is a commonly used experimental method to study the endocrine system of female animals, and it is also the best animal model to study PMOP. In this study, the preparation of the ovariectomized rat was confirmed through the detection of vaginal smear, the level of bone formation markers, and the analysis of bone tissue morphology. Transcriptome sequencing was used to analyze the molecular mechanism of PMOP in ovariectomized rats, qRT-PCR was used to verify the key targets. Results of Micro-CT and scanning electron microscopy (SEM) showed that the trabecular structure was disorganized and the symptoms of osteoporosis appeared, this indicating that the ovariectomized rats model was successfully prepared. Transcriptional sequencing results of femur tissue showed that 452 differentially expressed genes (DEGs) were screened. Bioinformatics analysis results showed that the osteoporosis caused by ovariectomized rats was mainly related to muscle contraction, calcium signaling pathway, etc. Results of qRT-PCR were consistent with transcriptome analysis. These results reveal the pathogenesis of PMOP in ovariectomized rats and also offer a possibility for elucidating the relevance of action between PMOP and sarcopenia. [ABSTRACT FROM AUTHOR]

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Background: Rotenone as a pesticide, damages the nervous system by oxidative stress. According to the published articles that reported the protective role of estrogen in the nervous system and resveratrol against oxidative stress, in this study, the protective effect of resveratrol was evaluated on oxidative stress factors induced by rotenone in hippocampus at present and absence of estrogen in female ovariectomized rats. Materials and Methods: Forty-eight female rats were respectively divided groups and treated with saline, rotenone, ovariectomized, resveratrol, ovariectomized+rotenone, ovariectomized+resveratrol, rotenone+resveratrol and ovariectomized+rotenone+resveratrol. Rotenone was administrated intraperitoneally and resveratrol was given orally every day for 21 days. At the end of experiment, malondialdehyde and glutathione level, catalase, and glutathione peroxidase activity in hippocampus were evaluated. Also, estrogen and progesterone in serum were measured. Results: Rotenone significantly decreased estrogen and progesterone. Furthermore, glutathione level and glutathione peroxidase and catalase activity reduced, while malondialdehyde significantly increased. Although, estrogen and progesterone and glutathione and catalase significantly decreased in ovariectomized group, but malondialdehyde significantly increased. Resveratrol could significantly increase estrogen and progesterone in resveratrol+rotenone and resveratrol+ovariectomized groups. It significantly increased glutathione, glutathione peroxidase and catalase in the intact ovariectomized rats that received rotenone, while reduced malondialdehyde in the rotenone, ovariectomized and ovariectomized+rotenone groups were observed. Conclusion: Resveratrol was able to reduce the oxidative stress which induced by rotenone and absence of estrogen in the hippocampal tissue of rats.

Objective To determine the effect of equol (Eq) intervention on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) in ovariectomized rats and investigate its mechanism of action. Methods Sixty 5-week-old female SD rats were randomly divided into 6 groups: sham group, ovariectomized+high-fat diet (OVX +HFD) group, OVX+HFD+low-, medium-, and high-dose Eq groups [20, 40 and 80 mg/(kg·d) Eq], and OVX+ HFD+estradiol group [E2, 0.25 mg/(kg·d)], with 8 rats in each group. After 12 weeks of intervention, the rats were sacrificed and sampled. The liver index was calculated and the serum levels of blood lipid TG, TC, HDL-C, LDL-C, FFA, liver function in indicators ALT, AST, inflammatory factors TNF-α, IL-6, estrogen, fasting insulin (FINS), fasting plasma glucose (FPG) and liver contents of TG, TC, TNF-α and IL-6 were detected. HE staining was used to observe the morphology of liver tissue. qRT-PCR and Western blotting was employed to detect the mRNA expression of TNF-α and IL-6 and the protein levels of NF-κB p-p65 in the liver tissues, respectively. Results Compared with the sham group, the OVX+HFD group had significantly decreased serum estrogen level (P < 0.05) and obvious hepatic steatosis, dyslipidemia, abnormal liver function and increased levels of inflammatory factors. Eq or E2 intervention resulted in notably increased serum estrogen and HDL-C levels, and remarkably reduced serum TG, TC, HDL-C, LDL-C, FFA, ALT, AST, TNF-α and IL-6 levels (P < 0.05), down-regulated expression of NF-κB p-p65, TNF-α and IL-6 in the liver tissues (P < 0.05), and certain improvements in steatosis of liver tissues when compared with the OVX+HFD group. Conclusion Eq intervention can effectively ameliorate high-fat diet-induced NAFLD in ovariectomized rats, and the mechanism may be partially associated with its inhibition on expression of inflammatory factors.

Background: Estrogen deficiency affects the structure and function of the salivary glands in women, leading to a decrease in salivary secretion and a change in the composition of saliva. Previous studies on changes in the salivary glands that cause estrogen deficiency have reported only partial results for the parotid and submandibular glands, and there are few comparative morphological studies of histological changes between the parotid and submandibular glands in ovariectomized rats (OVX) leading to estrogen deficiency. This study aimed to analyze the histopathological and histochemical changes in the parotid and submandibular salivary glands causing estrogen deficiency by using OVX, and to discuss the mechanism on these changes.Methods: The parotid and submandibular glands from sacrificed control and OVX groups were fixed with cold 4% paraformaldehyde in phosphate buffer (pH 7.2). The tissues were dehydrated using a series of graded ethyl alcohol and embedded in paraffin. For histopathological analysis, sections cut to a thickness of 6 to 7 µm were stained with hematoxylin and eosin (H&E). For histochemical analysis, Periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5), and PAS+AB (pH 2.5 and pH 1) staining was performed.Results: Histopathological analysis of OVX tissue showed that the parotid and submandibular salivary glands were broadly and clearly separated and divided into lobes. In OVX, acinar and ductal cells with condensed polymorphic or pyknotic nucleus, which are presumed to be characteristic of apoptotic cells, and degenerated cells with lipid deposition in cytoplasmic granules and ruptured membranes were increased. Histochemical analysis of OVX, confirmed an increase in the number and acidification of acinar secretory granules.Conclusion: Histopathological and histochemical changes and the effects of estrogen deficiency are more evident in the submandibular salivary gland than in the parotid gland.

Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that Zanthoxylum bungeanum seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and β-arrestin2 (βarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1β (IL-1β), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/βarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background/aim: We have evaluated the effects of taurine and aqueous garlic extract (AGE) as a dietary supplement on osteoporotic fracture (OPF) healing in the ovariectomized rat femur fracture model. Materials and methods: In this experimental animal study, twenty-four osteoporosis-remodeled female Wistar albino rats were randomly divided into 3 groups (n: 8) according to their supplemented diet; control, taurine, and AGE groups. Unilateral femur middiaphysis mini-open osteotomy was stabilized with Kirschner wires. Six weeks after osteotomy, the rats were sacrificed before the femurs were harvested and OPF healing was evaluated with biochemical, histologic, microcomputed-tomography, and scintigraphic methods. Results: As an indicator of the antiosteoporotic effect, the calcium levels of the taurine group were significantly lower than the AGE and control groups in biochemical analyzes (p < 0.01). In histological studies, the new bone diameter and new bone volume values of the taurine group were significantly higher than the control group (p = 0.002 and p = 0.032, respectively), while higher trabecular-compact callus was observed in the taurine and AGE groups, respectively, compared to the control group. In morphological analyses, taurine and AGE groups had significantly higher bone volume/tissue volume, trabecular number, bone surface density, and lower trabecular separation than the control group (p < 0.05). The scintigraphic imaging showed a significant increase in osteoblastic activity of the taurine group compared to the control group (p = 0.005). Conclusion: Taurine and AGE have positive anabolic effects, respectively, on the healing of OPFs, demonstrated by biochemical, histological, morphological, and scintigraphic methods. [ABSTRACT FROM AUTHOR]

Context: Yougui pill combined with Buzhong Yiqi decoction (YPBYD) is used to relieve sexual dysfunction in clinical practice. Objective: To investigate changes in microbial composition caused by sexual dysfunction and identify dominant bacteria related to YPBYD treatment. Materials and methods: Female Sprague-Dawley rats were randomly divided into four groups (n=6): one group underwent Sham operation (Sham group), while three groups underwent ovariectomy (one model and two treatment groups). The ovariectomized (OVX) rats received oestradiol benzoate (250 mg/kg/week) or YPBYD (3.6mL/d) via oral gavage for 4 weeks. Vaginal smear assay was performed; the serum levels of cyclic adenosine monophosphate (cAMP) and oestradiol (E2) were measured, followed by collection of stool samples for 16S rRNA sequencing. Results: After YPBYD treatment, the levels of E2 and cAMP in OVX rats significantly increased (E2: from 20.45 ± 1.60 ng/L to 24.38 ± 1.70 ng/L; cAMP: from 261.41 ± 9.21 pg/mL to 373.75 ± 17.37 pg/mL). OVX treatment decreased diversity of gut microbiota and YPBYD treatment restored gut microbiota composition. Compared with Sham group, the abundance of Romboutsia significantly increased, while those of Proteobacteria and Staphylococcus markedly decreased in OVX group (all p<0.05); meanwhile, the abundance of these microbes showed an opposite trend after YPBYD treatment. These microbiotas were involved in tyrosine and tryptophan biosynthesis and fatty acid metabolism. Discussion and conclusions: These findings are the first to indicate YPBYD can alleviate female sexual dysfunction by modulating gut microbiota in OVX rats, which will help enhance the understanding on potential mechanism of YPBYD against sexual dysfunction. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, ovariectomized rats are a mature and reliable animal model of osteoporosis, and establishment and observational evaluation of rat models of two types of kidney deficiency have been relatively detailed. However, further exploration is needed on the rat models of osteoporosis combined with syndromes of kidney-yang deficiency and kidney-yin deficiency. The sympathetic-parasympathetic nerve function test is used as a specific index to judge the syndrome of yin-deficiency and yang-deficiency, but this indicator is relatively insufficient for evaluating and analyzing the skeletal system of the two types of kidney-deficiency syndromes. “Integration of disease and syndrome” requires more experimental evidence and observational indicators. OBJECTIVE: To compare trabecular microstructure parameters and serum bone metabolism indicators between osteoporosis rat models of kidney-yang deficiency and kidney-yin deficiency METHODS: The ovaries of 20 female Spraque-Dawley rats were surgically removed to make postmenopausal osteoporotic rat models. Ten weeks after operation, all model rats were randomly divided into two groups (n=10 per group): kidney-yang deficiency group and kidney-yin deficiency group. Gluteal intramuscular injection of hydrocortisone and intragastric administration of thyroid hormone tablets were given to the kidney-yang deficiency group and the kidney-yin deficiency group, respectively, once a day for 14 consecutive days. After modeling, micro-CT was used to detect trabecular microstructure parameters in the region of interest of the left femur, and ELISA was used to detect serum bone formation and bone resorption indicators. RESULTS AND CONCLUSION: Two types of kidney-deficiency osteoporosis rat models were successfully established. Compared with the kidney-yang deficiency group, bone mineral density, bone volume/total volume, and trabecular number were significantly increased, trabecular thickness decreased, and serum bone formation and bone resorption indicators significantly increased in the kidney-yin deficiency group. Therefore, bone metabolism was faster in the kidney-yin deficiency group than the kidney-yang deficiency group. All these findings indicate significant differences in trabecular microstructure parameters and bone metabolism indicators between two kidney-yang and kidney-yin deficiency groups, and the mechanisms need to be further studied. [ABSTRACT FROM AUTHOR]

Objective To compare the therapeutic effects of psoralea corylifolia L. on osteoporosis in ovariectomized (OVX) rats before and after salt-processing, and to explore its processing mechanism. Methods OVX rat model received raw or salt-processed psoralea corylifolia L. by intragastric administration. After 12 weeks of continuous administration, the rats were weighed and taken the uterus. The serum contents of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin (OC), and estradiol (E2) were measured. The biomechanical strength and bone mineral density (BMD) were measured and the trabecular microstructure was observed. The drug-containing serum of raw and salt-processed psoralea corylifolia L. was prepared to detect its effect on the proliferation and differentiation of osteoblasts. The content of main effective components of water decoction and drug-contained serum was measured. Results Both raw and salt-processed psoralea corylifolia L.effectively inhibited the weight gain and uterine atrophy of ovariectomized rats, increased the contents of serum Ca and P, decreased the contents of ALP, OC and E2, significantly increased bone mineral density and bone biomechanical strength, and improved the integrity of bone trabecular structure. Raw and salt-processed psoralea corylifolia L. had obvious stimulating effects on the proliferation and differentiation of osteoblasts, and the effect of salt products is better than that of raw one. In addition, there were significant differences in the contents of active components between water decoction and serum after salt-processing. Conclusion Raw and salt-processed psoralea corylifolia L. have a good therapeutic effect on osteoporosis induced by OVX in rats. The salt products have better anti-osteoporosis effect. It is related to the process of salt-processing which may promote the decoction of glycosides, such as psoralenoside and isopsoralenoside. After salt-processing, the effective components may be absorbed more into blood, such as psoralen and isopsoralen. [ABSTRACT FROM AUTHOR]

BACKGROUND: Zoledronic acid is a classical bisphosphate bone resorption inhibitor; however, its effect and mechanism on the mandibular alveolar bone metabolism are not clarified. OBJECTIVE: To study the effects of zoledronic acid on the expression of bone resorption and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the mandibular alveolar bone of ovariectomized osteoporosis rats. METHODS: Thirty-six female Sprague-Dawley rats were randomly divided into three groups (n=12 per group): sham group, osteoporosis group (bilateral ovariectomy), and zoledronic acid group (bilateral ovariectomy, followed by administration of zoledronic acid). Twelve weeks after ovariectomy, the rats in the zoledronic acid group were given subcutaneous injection of 20 μg/kg zoledronic acid, and the corresponding doses of saline were injected subcutaneously in the sham and osteoporosis groups. The rat's mandibular alveolar bone was separated and removed at 4 weeks after administration. Alveolar bone mass band alveolar bone absorption were observed by Micro-CT, the pathological changes of the alveolar bone were observed using hematoxylin-eosin staining, the number of osteoclasts in alveolar bone was observed by tartrate resistant acid phosphatase staining, the expression of NLRP3 was determined by immunohistochemical technique, and the protein levels of NLRP3, Caspase-1, and interleukin-1β in the alveolar bone were detected using western blot. RESULTS AND CONCLUSION: Compared with the sham group, the bone trabecular structure was broken in the osteoporosis group, with the emergence of a large number of bone resorption lacunae and uneven surface of the alveolar bone; meanwhile, percent bone volume, trabecular thickness, bone mineral density in alveolar bone were lower, trabecular separation were increased, and the number of osteoclast was significantly increased in the osteoporosis group (P < 0.05). Compared with the osteoporosis group, alveolar bone microstructure in the zoledronic acid group was improved, and the above pathological symptoms were alleviated obviously. Immunohistochemistry staining results showed that the expression level of NLRP3 protein was significantly higher in the osteoporosis group than the sham group (P < 0.05), and the expression of NLRP3 was significantly lower in the zoledronic acid group than the osteoporosis group (P < 0.05). Western blot results indicated that the expression levels of NLRP3, Caspase-1 and interleukin-1β proteins was higher in the osteoporosis group than the sham group, while the protein levels in the zoledronic acid were lower than those in the osteoporosis group (P < 0.05). To conclude, zoledronic acid can effectively inhibit the expression of NLRP3, Caspase-1 and inteleukin-1β in the alveolar bone of osteoporotic rats, and inhibit mandibular alveolar bone resorption by reducing the number of osteoclasts. [ABSTRACT FROM AUTHOR]

Abstract Background Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. Methods In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl’s staining. The expressions of β-CTX and osteocalcin were assessed by ELISA. Results It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. Conclusions In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.

Abstract Background Post-menopausal osteoporosis is a concern of health organizations, and current treatments do not seem enough. Postbiotics as bioactive compounds produced by probiotics may be an attractive alternative for bone health. In this study, we prepared, formulated, and compared the effects of cell lysate and supernatant of five native probiotic strains (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) in ovariectomized (OVX) rats. Methods The probiotic strains were isolated, and their cell-free supernatants and biomasses as postbiotics were extracted and formulated using standard microbial processes. The Sprague-Dawley rats were fed by 1 × 109 CFU/ml/day postbiotic preparations for 4 weeks immediately after ovariectomy. Dual-energy X-ray absorptiometry (DEXA) scans were accomplished to evaluate femur, spine, and tibia BMD. The serum biochemical markers [calcium, phosphorus, and alkaline phosphatase] were assessed. Results Postbiotics could considerably improve the global and femur area in OVX rats. In the case of global bone mineral density (BMD), Lactobacillus casei lysate and supernatant, Bacillus coagulans lysate and supernatant, lysate of Bifidobacterium longum and Lactobacillus acidophilus, and Lactobacillus reuteri supernatant significantly increased BMD. We found Bacillus coagulans supernatant meaningfully enriched tibia BMD. Conclusion Postbiotic could ameliorate bone loss resulting from estrogen deficiency. Also, the effects of postbiotics on different bone sites are strain-dependent. More clinical studies need to explore the optimal administrative dose and duration of the specific postbiotics in protecting bone loss.

The study aimed to investigate the relieving effect of QingYan Formula (QYF) in treating perimenopausal syndrome. A combination of metabonomic analysis and in vitro pharmacodynamic experiments was employed to achieve this objective.Over a period of 12 weeks, ovariectomized (OVX) rats were orally administered QYF's 70 % ethanol extract or estradiol valerate (EV). The results demonstrate that QYF restored the estrous cycle of ovariectomized rats and exhibited significant estrogenic activity, as indicated by reversal of uterine and vagina atrophy, improvement of serum estradiol level and decrease of serum luteinizing hormone(LH) level. Additionally, QYF administration effectively reduced high bone turnover and repaired trabecular microstructure damage. Metabonomic analysis of the OVX rats treated with QYF revealed the identification of 55 different metabolites in the serum, out of which 35 may be potential biomarkers. QYF could regulate the disturbed metabolic pathways including the Biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, bile secretion, and steroid hormone biosynthesis. PI3KCA, SRC, and MAPK3 are potential therapeutic targets for QYF therapeutic effects. These findings support the efficacy of QYF in alleviating perimenopausal syndrome and regulating lipid metabolic disorders in OVX rats. • This study explore QingYan Formula (QYF)'s effect on ovariectomized rats. • QYF alienates MPS mainly by regulating metabolites in lipid pathway. • The metabolites were correlated with hormones and bone metabolism indexes. [ABSTRACT FROM AUTHOR]

The role of 17β‐estradiol (E2) in high‐fat diet (HFD)‐induced alteration of the protein kinase B (Akt) signaling pathway in ovariectomized (OVX) rats is unclear. Therefore, we examined whether chronic estrogen replacement restores HFD‐induced impairment in insulin sensitivity by its effects concomitant with alterations in the Akt isoform 2 (Akt2) and Akt substrate of 160 kDa (AS160) phosphorylation in muscles of OVX rats. Nine‐week‐old female Wistar rats underwent ovariectomy under anesthesia; after 4 weeks, subcutaneous implantation of either E2 or placebo (PL) pellets was performed, and HFD feeding was initiated. Intravenous glucose tolerance tests were performed to assess insulin sensitivity. Following insulin injection into rats' portal vein, the liver and gastrocnemius muscle were dissected for insulin signaling analysis. We observed that HFD increased energy intake and body weight in the PL group; however, it was temporarily decreased in the E2 group. Adipose tissue accumulation was larger in HFD‐fed rats than in normal chow diet (NCD)‐fed rats in the PL group; however, this difference was not observed in the E2 group. HFD reduced insulin sensitivity in the PL group only. In vivo insulin stimulation increased Akt2 phosphorylation in the muscles of NCD‐fed rats in both groups. In contrast, HFD affected insulin‐stimulated phosphorylation of Akt2 and AS160 in the muscles of rats in the PL group but not in the E2 group. Our data suggest that E2 replacement improves HFD‐induced insulin resistance, and this effect is accompanied by the alterations in the Akt2 and AS160 phosphorylation in insulin‐stimulated muscles of OVX rats. [ABSTRACT FROM AUTHOR]

Abstract The role of 17β‐estradiol (E2) in high‐fat diet (HFD)‐induced alteration of the protein kinase B (Akt) signaling pathway in ovariectomized (OVX) rats is unclear. Therefore, we examined whether chronic estrogen replacement restores HFD‐induced impairment in insulin sensitivity by its effects concomitant with alterations in the Akt isoform 2 (Akt2) and Akt substrate of 160 kDa (AS160) phosphorylation in muscles of OVX rats. Nine‐week‐old female Wistar rats underwent ovariectomy under anesthesia; after 4 weeks, subcutaneous implantation of either E2 or placebo (PL) pellets was performed, and HFD feeding was initiated. Intravenous glucose tolerance tests were performed to assess insulin sensitivity. Following insulin injection into rats’ portal vein, the liver and gastrocnemius muscle were dissected for insulin signaling analysis. We observed that HFD increased energy intake and body weight in the PL group; however, it was temporarily decreased in the E2 group. Adipose tissue accumulation was larger in HFD‐fed rats than in normal chow diet (NCD)‐fed rats in the PL group; however, this difference was not observed in the E2 group. HFD reduced insulin sensitivity in the PL group only. In vivo insulin stimulation increased Akt2 phosphorylation in the muscles of NCD‐fed rats in both groups. In contrast, HFD affected insulin‐stimulated phosphorylation of Akt2 and AS160 in the muscles of rats in the PL group but not in the E2 group. Our data suggest that E2 replacement improves HFD‐induced insulin resistance, and this effect is accompanied by the alterations in the Akt2 and AS160 phosphorylation in insulin‐stimulated muscles of OVX rats.

Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that Zanthoxylum bungeanum seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and β-arrestin2 (βarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1β (IL-1β), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/βarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases.

Background and Aim: Both virgin coconut oil (VCO) and tocotrienol-rich fraction (TRF) are rich in antioxidants and may protect the bone against bone loss induced by ovariectomy and high-fat diet. The study aimed to determine the protective effects of combined therapy of VCO and TRF on osteoporosis in ovariectomized (OVX) rat fed with high-fat diet. Materials and Methods: Thirty-six female Sprague-Dawley rats were divided into six groups: Sham-operated (SHAM), OVX control, OVX and given Premarin at 64.5 μg/kg (OVX+E2), OVX and given VCO at 4.29 ml/kg (OVX+V), OVX and given TRF at 30 mg/kg (OVX+T), and OVX and given a combination of VCO at 4.29 ml/kg and TRF at 30 mg/kg (OVX+VT). Following 24 weeks of treatments, blood and femora samples were taken for analyses. Results: There were no significant differences in serum osteocalcin levels between the groups (p>0.05), while serum C-terminal telopeptide of Type I collagen levels of the OVX+VT group were significantly lower than the other groups (p

Background: Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. Methods: In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl's staining. The expressions of β-CTX and osteocalcin were assessed by ELISA. Results: It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. Conclusions: In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption. [ABSTRACT FROM AUTHOR]

Indigestible sugars are used in food production and pharmaceutical industry due to their desirable properties. The effects of mannitol on Ca and Mg absorption and retention in ovariectomized rats were evaluated. Five weeks old ovariectomized Wistar rats were given Ca, Mg-deficient diet for 28 days then fed a control diet or 8% mannitol diets for another 28 days. Feaces were collected twice for 72h to measure mineral absorption. On day 56, rats were slaughtered and cecal parameters were observed. Femurs were collected to measure mineral levels. Results were shown that mineral absorption and femoral mineral was significantly increased by mannitol feeding. Cecal parameters were significantly altered after mannitol consumption. In conclusion, Ca and Mg absorption and their retention were improved by cecal fermentation of mannitol in ovariectomized rats.

Context: Evidence suggests that microRNA (miRNA) regulates gene expression and bone tissue homoeostasis of osteoporosis. MiR-152 has found to be abnormally expressed in osteoporosis, but its role in osteoblast differentiation has not been elucidated. Objective: To understand the potential mechanism of miR-152 in osteoblast differentiation via regulation of RICTOR. Materials and methods: The expression of miR-152 and RICTOR were tested in ovariectomized rat models of osteoporosis. Primary osteoblasts and MC3T -E1 cells were assigned into four groups, namely Control, miR-152 inhibitor, miR-control and miR-152 inhibitor + siRICTOR groups. qRT PCR and Western blots were performed to detect the expression of miR-152 and RICTOR, respectively. MTT assay was used to evaluate cell viability, and ALP activity determination and mineralization analyses were also conducted. Results: In ovariectomy-induced osteoporotic rats, miR-152 (3.06 ± 0.35) in femoral tissues increased significantly, while RICTOR (0.31 ± 0.04) decreased. Compared with the Control group, the miR-152 inhibitor group presented appreciable reduction of miR-152 in primary osteoblasts and MC3T3-E1 cells, as well as remarkable increases in RICTOR, p-Akt(s473)/Akt ratio, and osteogenesis-related genes, with enhanced cell viability, ALP activity and mineralization. In comparison with cells in the miR-152 inhibitor group, those in the miR-152 inhibitor + siRICTOR group had no observable difference in miR-152, but were dramatically up-regulated in RICTOR, as well as the corresponding opposite tendencies of other factors. Conclusion: Inhibiting miR-152 promoted osteoblasts differentiation and alleviated osteoporosis by up-regulating RICTOR. Therefore, miR-152 may be an essential mediator of osteoblast differentiation and a new therapeutic strategy for osteoporosis.

Menopausal women are susceptible to have high risk of cardiovascular diseases, type II diabetes and osteoporosis due to the metabolic disorder caused by estrogen deficiency. Accumulating evidence supports that gut microbiota is a key regulator of metabolic diseases. Our previous metabolomics study interestingly demonstrated that the anti-osteoporotic effects of lignan-rich fraction (SWCA) from Sambucus wialliamsii Hance were related to the restoration of a series of lipid and glucose metabolites. This study aims to investigate how SWCA modulates lipid and glucose metabolism and the underlying mechanism. Our results show that oral administration of SWCA (140 mg/kg and 280 mg/kg) for 10 weeks alleviated dyslipidemia, improved liver functions, prevented glucose tolerance and insulin actions, attenuated system inflammation and improved intestinal barrier in OVX rats. It also induced a high abundance of Actinobacteria, and restored microbial composition. We are the first to report the protective effects of the lignan-rich fraction from S. williamsii on dyslipidemia and insulin resistance. Our findings provide strong evidence for the application of this lignan-rich fraction to treat menopausal lipid disorder and insulin resistance-related diseases.

Background: Post-menopausal osteoporosis is a concern of health organizations, and current treatments do not seem enough. Postbiotics as bioactive compounds produced by probiotics may be an attractive alternative for bone health. In this study, we prepared, formulated, and compared the effects of cell lysate and supernatant of five native probiotic strains (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) in ovariectomized (OVX) rats. Methods: The probiotic strains were isolated, and their cell-free supernatants and biomasses as postbiotics were extracted and formulated using standard microbial processes. The Sprague-Dawley rats were fed by 1 × 109 CFU/ml/day postbiotic preparations for 4 weeks immediately after ovariectomy. Dual-energy X-ray absorptiometry (DEXA) scans were accomplished to evaluate femur, spine, and tibia BMD. The serum biochemical markers [calcium, phosphorus, and alkaline phosphatase] were assessed. Results: Postbiotics could considerably improve the global and femur area in OVX rats. In the case of global bone mineral density (BMD), Lactobacillus casei lysate and supernatant, Bacillus coagulans lysate and supernatant, lysate of Bifidobacterium longum and Lactobacillus acidophilus, and Lactobacillus reuteri supernatant significantly increased BMD. We found Bacillus coagulans supernatant meaningfully enriched tibia BMD. Conclusion: Postbiotic could ameliorate bone loss resulting from estrogen deficiency. Also, the effects of postbiotics on different bone sites are strain-dependent. More clinical studies need to explore the optimal administrative dose and duration of the specific postbiotics in protecting bone loss. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the changes in circulating microRNA (miRNA) expression profiles associated with the potential osteoprotective effect of diosgenin (DIO) in ovariectomized (OVX) rats. Wistar rats (female) were subjected to a sham operation (SHAM group) or ovariectomy. OVX rats were treated with DIO (DIO group) or vehicle (OVX group) for 12 weeks. Following treatment, the serum estradiol, bone turnover biomarker levels, and the microarchitecture of tibias were assayed. Based on miRNA microarray and qRT-PCR analyses, differentially expressed (DE) circulating miRNAs were identified between the OVX and SHAM groups (comparison A) and between the DIO and OVX groups (comparison B). Furthermore, putative target genes of shared DE miRNAs with opposite expression trends in the two comparisons were predicted by ingenuity pathway analysis (IPA). Finally, the expression levels of the putative target genes in serum and tibia were validated by qRT-PCR. The micro-CT results demonstrated that DIO had a substantial anti-osteopenic effect on the tibias of OVX rats. In total, we found 5 DE circulating miRNAs (four upregulated and one downregulated) in comparison A and 21 DE circulating miRNAs (15 upregulated and 6 downregulated) in comparison B. However, only one DE circulating miRNA (rno-miR-20a-5p) had opposite expression trends between the two comparisons. Including rno-miR-20a-5p, 7 of the 10 selected DE circulating miRNAs between the two comparisons passed qRT-PCR validation. Specifically, based on qRT-PCR validation, DIO upregulated the expression of rno-miR-20a-5p and downregulated that of three target genes (Tnf, Creb1, and Tgfbr2) of the “osteoclast differentiation” pathway in the tibias of OVX rats. Our results suggested that DIO could change the circulating miRNA profile of OVX rats and inhibited the downregulation of miR-20a-5p in serum and tibia. DIO might exert an anti-osteoclastogenic effect on OVX rats by upregulating the expression of miR-20a-5p in circulation and bone tissue.

Introduction: Osteoporosis can produce a persistent state of pain known as osteoporotic pain. One proposed mechanism of this pathology is increased calcitonin gene-related peptide (CGRP; a marker related to inflammatory pain) expression in the dorsal root ganglia (DRG) innervating osteoporotic vertebrae. Alternatively, a previous study revealed that axial loading caused osteoporotic pain in a rodent model of coccygeal vertebrae compression. Because this compression model is associated with trauma, additional mechanistic studies of osteoporotic pain in the absence of trauma are required. The current study aimed to evaluate the expression and relative distribution of transient receptor potential vanilloid 4 (TRPV4), a pain-related mechanoreceptor, in ovariectomized (OVX) osteoporotic rats. Methods: CGRP-immunoreactive (-ir) and TRPV4-ir DRG neurons innervating the L3 vertebrae of Sprague-Dawley rats were labeled with a neurotracer, FluoroGold. Intravertebral pH was also measured during the neurotracer procedure. TRPV4-ir/CGRP-ir FluoroGold-positive DRG neurons were quantified in sham control and OVX rats (n = 10, ea). The threshold for statistical significance was set at P < 0.05. Results: There was no statistical difference in the number of FluoroGold-positive DRG neurons between groups; however, there were significantly more CGRP-ir/TRPV4-ir FluoroGold-positive DRG neurons in the OVX group compared with the sham control group (P < 0.05) as well as the significantly increased molecular production of each peptide. Intravertebral pH was also lower in the OVX group compared with the sham control group (P < 0.05). Conclusion: Sensory neurons innervating osteoporotic vertebrae exhibited increased expression of co-localized CGRP and TRPV4 in OVX osteoporotic rats. Additionally, intravertebral pH was low in the vicinity osteoporotic vertebrae. Considering that TRPV4 is a mechanosensitive nociceptor that is activated in acidic environments, its upregulation may be associated with the pathology of osteoporotic pain derived from microinflammation involved in osteoporosis.

Background & Objectives: Menopause is associated with increased cardiovascular risk factors. This investigation examined the effects of resistance training on cardiovascular risk factors in ovariectomized rats. Material & methods: In this experimental study, 16 adult ovariectomized female Wistar rats were randomly allocated into control (n=8) and resistance training (n=8) groups. The progressive resistance training protocol was administered for 10 weeks (5 sessions per weeks). Training protocol consisted of 8 series of climbs on the ladder with progressive overload attached to the tail and each series contained an average of 8 to 12 climbing movements (repetitions). Forty eight hours after the last training session, animals were anesthetized, blood was taken directly from the heart. Then serum homocysteine levels and lipid profile were measured and insulin resistance index was calculated. All variables were compared by unpaired t-test) p< 0.05(. Results: serum homocysteine levels (p = 0.013) and insulin resistance index (p = 0.019) were significantly decreased in resistance training group compared with the control group, but lipid profile did not differ among rat groups (p˃0.05). Conclusion: It seems that ten weeks of progressive resistance training reduced serum homocysteine levels and insulin resistance index in ovariectomized rats, but did not effect on the serum lipid profile.

BACKGROUND: Although zoledronic acid can effectively prevent bone loss in postmenopausal women, its effect and mechanism on the mandible are not clarified. OBJECTIVE: To study the morphological and pathological changes of mandibular tissue in ovariectomized rats treated with low-dose zoledronic acid and to investigate the regulatory effect and mechanism of RANKL/RANK/OPG signaling system in the inhibition of bone resorption by zoledronic acid. METHODS: Thirty-six adult female Sprague-Dawley rats were randomized into control, model and treatment groups. Animal models of osteoporosis were made by bilateral ovariectomy in the latter two groups, while the same amount of lipid tissues surrounding the ovary was removed in the control group. Three weeks after ovariectomy, the rats in the treatment group were given subcutaneous injection of 20 μg/kg zoledronic acid. The corresponding doses of saline were injected subcutaneously in the control and model groups. One week after treatment, the left mandibular molars were extracted from all the rats, and the rats’ jaws were separated and removed at 4 weeks after tooth extraction for detection. The residual alveolar bone of the extracted socket was observed by X-ray. The pathological changes of the mandibular cortex and cancellous bone were detected by hematoxylin-eosin staining. The number of apoptotic osteoblasts was detected by TUNEL apoptosis test. The expressions of receptor activator of nuclear factor-κ B ligand (RANKL), osteoprotegerin and nuclear transcription factor-κB (NF-κB) in the mandibular alveolar bone were detected by immunohistochemical technique. Western blot was finally used to detect the expression of RANKL and NF-κB at protein levels. RESULTS AND CONCLUSION: (1) At 4 week after tooth extract, subcutaneous injection of 20 μg/kg zoledronic acid effectively inhibited alveolar bone resorption and promoted new bone formation at the extraction socket. (2) Hematoxylin-eosin staining results showed that: in the model group, the cortical bone was thinned, and the trabecular bone was thinned and even ruptured. There were a large number of bone resorption lacunae but few osteoblasts in the model group. In the treatment group, the cortical bone was thickened and the trabecular bone had normal structure, with only a small amount of bone resorption lacunae and increased number of osteoblasts. (3) The number of apoptotic osteoblasts was significantly lower in the treatment group than the model group (P < 0.001). (4) Immunohistochemical staining results showed significantly decreased RANKL and NF-κB protein expressions (P < 0.001, P < 0.002) and significantly increased osteoprotegerin level (P < 0.001) in the treatment group than the model group. (5) Western blot results revealed that the protein expressions of RANKL and NF-κB in the model group were significantly higher than those in the control group, and treatment with zoledronic acid significantly reduced these protein levels (both P < 0.001). To conclude, zoledronic acid could inhibit the differentiation of osteoclasts by down-regulating the NF-κB signal pathway and meanwhile regulate the apoptosis of osteoblasts. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the changes in circulating microRNA (miRNA) expression profiles associated with the potential osteoprotective effect of diosgenin (DIO) in ovariectomized (OVX) rats. Wistar rats (female) were subjected to a sham operation (SHAM group) or ovariectomy. OVX rats were treated with DIO (DIO group) or vehicle (OVX group) for 12 weeks. Following treatment, the serum estradiol, bone turnover biomarker levels, and the microarchitecture of tibias were assayed. Based on miRNA microarray and qRT-PCR analyses, differentially expressed (DE) circulating miRNAs were identified between the OVX and SHAM groups (comparison A) and between the DIO and OVX groups (comparison B). Furthermore, putative target genes of shared DE miRNAs with opposite expression trends in the two comparisons were predicted by ingenuity pathway analysis (IPA). Finally, the expression levels of the putative target genes in serum and tibia were validated by qRT-PCR. The micro-CT results demonstrated that DIO had a substantial anti-osteopenic effect on the tibias of OVX rats. In total, we found 5 DE circulating miRNAs (four upregulated and one downregulated) in comparison A and 21 DE circulating miRNAs (15 upregulated and 6 downregulated) in comparison B. However, only one DE circulating miRNA (rno-miR-20a-5p) had opposite expression trends between the two comparisons. Including rno-miR-20a-5p, 7 of the 10 selected DE circulating miRNAs between the two comparisons passed qRT-PCR validation. Specifically, based on qRT-PCR validation, DIO upregulated the expression of rno-miR-20a-5p and downregulated that of three target genes (Tnf , Creb1 , and Tgfbr2) of the "osteoclast differentiation" pathway in the tibias of OVX rats. Our results suggested that DIO could change the circulating miRNA profile of OVX rats and inhibited the downregulation of miR-20a-5p in serum and tibia. DIO might exert an anti-osteoclastogenic effect on OVX rats by upregulating the expression of miR-20a-5p in circulation and bone tissue. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has a high incidence in postmenopausal women and is accompanied by insulin resistance, obesity, and dyslipidemia. Royal jelly (RJ), a natural substance derived from hive, possesses numerous health‐beneficial properties. Here, we evaluated the effects of RJ (150, 300, and 450 mg kg–1 day–1, 8 weeks) on NAFLD in ovariectomized (OVX) rats. Based on the results, RJ ameliorated the degree of anxiety, improved serum lipid profile, and attenuated the hepatic steatosis and liver injury in OVX rats. Furthermore, the protective effects of RJ could be attributed to its antioxidant properties, which enhance the levels of hepatic antioxidant enzymes. The qRT‐PCR results also suggest that RJ improves the disturbances of circadian genes by downregulating their expression, including that of Per1 and Per 2, in the liver of OVX rats. Altogether, our findings suggest that RJ may be a promising agent for the treatment of NAFLD. Practical applications: Postmenopausal women are at an increased risk of NAFLD. Currently, there are no licensed therapies for NAFLD. Although hormone replacement therapy (HRT) is reported to inhibit the development of NAFLD, it causes unexpected adverse effects. As HRT is controversial, the use of natural supplements to counteract the detrimental effects of menopause has recently attracted more attention. RJ is a natural product secreted from the hypopharyngeal and mandibular glands of worker bees. The present study illustrates the protective effect of the natural product, RJ, and its underlying mechanisms on NAFLD. This is the first study to assess the effect of RJ on NAFLD under estrogen deficiency. Such findings contribute to the further utilization of RJ, which might serve as a promising therapeutic option and natural food for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Epigallocatechin‐3‐O‐gallate (EGCG) exists as one of the major active components of green tea and has been studied extensively; however, the relationship between EGCG and the changes in the gut microflora of ovariectomized (OVX) rats as a model of menopause women have not yet been studied. Female Wistar rats were fed on a maintenance material diet and underwent either ovariectomy or SHAM surgery. The ovariectomized rats were divided into OVX group with the treatment of placebo or EGCG group which was treated with EGCG by oral gavage. After 8 weeks of treatment, anxiety‐like behaviors were assessed using elevated plus maze test (EMP) and open field test (OFT). The serum estradiol concentration was assayed through ELISA. High‐throughput V3–V4 16S rDNA sequencing was conducted to assess the microbial diversity in fecal samples collected from all rats. EGCG, at a concentration of 10 mg/kg, caused behavioral changes in rats similar to anxiety. In EPM, OVX rats spent less time in open arms than SHAM group rats and EGCG group rats (F = 16.043, p <.01). In OFT, the total travelled distance and the number of entries for EGCG group were higher compared with OVX group (F = 30.939, H = 13.107, respectively; p <.01). In addition, the distribution and composition of intestinal microflora in rats changed after ovariectomy. EGCG modulated the diversity of gut microbiota in OVX group at the phylum and the genus levels. Our results suggested that the composition of gut microbiota and anxiety in OVX rats were simultaneously affected by EGCG, and therefore, the two conditions might be strongly related, yet the deeper mechanistic links need further exploration. [ABSTRACT FROM AUTHOR]

The development of postmenopausal osteoporosis is thought to be closely related to oxidative stress. Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase (SOD) mimetic, could protect osteoblasts from cytotoxicity and dysfunction caused by oxidative stress. However, it is still unclear whether MnTBAP has effect on the development of postmenopausal osteoporosis. Here, we demonstrated that MnTBAP can inhibit bone mass loss and bone microarchitecture alteration, and increase the number of osteoblasts while reducing osteoclasts number, as well as improve the BMP-2 expression level in ovariectomized rat model. Additionally, MnTBAP can also prevent oxidative stress status up-regulation induced by ovariotomy and hydrogen peroxide (H2O2). Furthermore, MnTBAP reduced the effect of oxidative stress on osteoblasts differentiation and increased BMP-2 expression levels with a dose-dependent manner, via reducing the levels of mitochondrial oxidative stress in osteoblasts. Taken together, our findings provide new insights that MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts, and maybe a potential drug in postmenopausal osteoporosis therapy. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing importance of memory impairment in menopause, the current therapy against memory impairment in menopause is still limited. Therefore, the novel memory enhancer for menopause is required. Based on the crucial roles of oxidative stress and cholinergic function on memory and the synergistic concept, the memory enhancing effect of the polyherbal chicken soup which contains many herbs possessing antioxidant effect has gained attention. However, no supported evidence is available until now. Objective: To assess the memory enhancing effect of the polyherbal chicken soup (WO1) and to determine the possible underlying mechanism in animal model of menopause. Materials and Methods: Female Wistar rats were divided in to 6 groups: 1) sham plus vehicle, 2) OVX plus vehicle, 3) OVX plus isoflavone, 4 to 6) OVX plus WO1 at doses of 0.8, 1.6 and 2.4 mg.kg-1 respectively. All rats were treated with the assigned substance for 35 days and memory assessment was performed every 7 days throughout the study period. Then, they were determined malondialdehyde (MDA) level together with the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and acetylcholinesterase (AChE) in hippocampus at the end of experiment. Results: All doses of WO1 improved memory and decreased both AChE activity and MDA level in hippocampus of OVX rats. The enhanced SOD activity was observed in all WO1 treatment groups but the increased CAT and GPX activities were observed only in high dose treatment group. Conclusion: WO1 can improve memory in experimental menopause. The mechanism may occur partly via the improvement of cholinergic function and oxidative status in hippocampus. Our data suggest that WO1 is the potential functional food targeting at memory enhancement for menopausal women. However, clinical study is still essential to confirm aforementioned health benefit. [ABSTRACT FROM AUTHOR]

Bisphosphonates (BPs) and teriparatide (TPTD) are both effective treatments for osteoporosis, but BP treatment prior to daily TPTD treatment has been shown to impair the effect of TPTD in some clinical studies. In contrast, the loss of bone mineral density (BMD) that occurs after withdrawal of TPTD can be prevented by BP treatment. Although various studies have investigated the combination and/or sequential use of BP and TPTD, there have been no clinical studies investigating sequential treatment with zoledronic acid (ZOL) and TPTD (or vice versa). In this study, we evaluated the effects of sequential treatment with TPTD followed by ZOL, and ZOL followed by TPTD, using ovariectomized (OVX) rats. Two months after OVX, osteopenic rats were treated with ZOL, TPTD, or vehicle for a period of 4 months (first treatment period), and then the treatments were switched and administered for another 4 months (second treatment period). The group treated with ZOL followed by TPTD showed an immediate increase in BMD of the proximal tibia and greater BMD and bone strength of the lumbar vertebral body, femoral diaphysis, and proximal femur than the group treated with ZOL followed by vehicle. Serum osteocalcin, a marker of bone formation, increased rapidly after switching to TPTD from ZOL. The group treated with TPTD followed by ZOL did not lose BMD in the proximal tibia after TPTD was stopped, while the group treated with TPTD followed by vehicle did lose BMD. The BMD and bone strength of the lumbar vertebral body, femoral diaphysis, and proximal femur were greater in the group treated with TPTD followed by ZOL than in the group treated with TPTD followed by vehicle. The increase in serum osteocalcin and urinary CTX after withdrawal of TPTD was prevented by the switch from TPTD to ZOL. In conclusion, our results demonstrate that switching from ZOL to TPTD resulted in a non-attenuated anabolic response in the lumbar spine and femur of OVX rats. In addition, switching from TPTD to ZOL caused BMD to be maintained or further increased. If these results can be reproduced in a clinical setting, the sequential use of ZOL followed by TPTD or vice versa in the treatment of osteoporosis patients would contribute to increases in BMD that, hopefully, would translate into a corresponding decrease in the incidence of vertebral and non-vertebral fractures.

Background and Aim: Both virgin coconut oil (VCO) and tocotrienol-rich fraction (TRF) are rich in antioxidants and may protect the bone against bone loss induced by ovariectomy and high-fat diet. The study aimed to determine the protective effects of combined therapy of VCO and TRF on osteoporosis in ovariectomized (OVX) rat fed with high-fat diet. Materials and Methods: Thirty-six female Sprague-Dawley rats were divided into six groups: Sham-operated (SHAM), OVX control, OVX and given Premarin at 64.5 µg/kg (OVX+E2), OVX and given VCO at 4.29 ml/kg (OVX+V), OVX and given TRF at 30 mg/kg (OVX+T), and OVX and given a combination of VCO at 4.29 ml/kg and TRF at 30 mg/kg (OVX+VT). Following 24 weeks of treatments, blood and femora samples were taken for analyses. Results: There were no significant differences in serum osteocalcin levels between the groups (p>0.05), while serum C-terminal telopeptide of Type I collagen levels of the OVX+VT group were significantly lower than the other groups (p<0.05). The dynamic bone histomorphometry analysis of the femur showed that the double-labeled surface/bone surface (dLS/BS), mineral apposition rate, and bone formation rate/BS of the OVX+E2, OVX+T, and OVX+VT groups were significantly higher than the rest of the groups (p<0.05). Conclusion: A combination of VCO and TRF has the potential as a therapeutic agent to restore bone loss induced by ovariectomy and high-fat diet. [ABSTRACT FROM AUTHOR]

Context: Evidence suggests that microRNA (miRNA) regulate gene expression and bone tissue homoeostasis of osteoporosis. MiR-152 has found to be abnormally expressed in osteoporosis, but its role in osteoblast differentiation has not been elucidated. Objective: To understand the potential mechanism of miR-152 in osteoblast differentiation via regulation of RICTOR. Materials and methods: The expression of miR-152 and RICTOR were tested in ovariectomized rat models of osteoporosis. Primary osteoblasts and MC3T -E1 cells were assigned into four groups, namely Control, miR-152 inhibitor, miR-control and miR-152 inhibitor + siRICTOR groups. qRT PCR and Western blot were performed to detect the expressions of miR-152 and RICTOR, respectively. MTT assay was used to evaluate cell viability, and ALP activity determination and mineralization analyses were also conducted. Results: In ovariectomy-induced osteoporotic rats, miR-152 (3.06 ± 0.35) in femoral tissues increased significantly, while RICTOR (0.31 ± 0.04) decreased. Compared with Control group, miR-152 inhibitor group presented appreciable reduction of miR-152 in primary osteoblasts and MC3T3-E1 cells, as well as remarkable increases in RICTOR, p-Akt(s473)/Akt ratio, and osteogenesis-related genes, with enhanced cell viability, ALP activity and mineralization. In comparison with cells in the miR-152 inhibitor group, those in the miR-152 inhibitor + siRICTOR group had no observable difference in miR-152, but were dramatically up-regulated in RICTOR, as well as the corresponding opposite tendencies of other factors. Conclusion: Inhibiting miR-152 promoted osteoblasts differentiation and alleviated osteoporosis by up-regulating RICTOR. Therefore, miR-152 may be an essential mediator of osteoblast differentiation and a new therapeutic strategy for osteoporosis. [ABSTRACT FROM AUTHOR]

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called “Man HyungJa” in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

Background: We aimed to elucidate the preventive effects of taurine against osteopenia in ovariectomized (OVX) rats and the mechanisms by which taurine regulates osteoblastogenesis in vitro and in vivo. Methods: The effects of the taurine on human osteoblast MG-63 cell differentiation and osteoblastogenesis effect in OVX rat were examined Konkuk University in 2018 by evaluating osteoblast differentiation, and expression of osteoblast-specific factors by western blotting analysis. Results: Taurine supplementation significantly improved alkaline phosphatase (ALP) activity and mineralization in a concentration-dependent manner. Further, taurine induced the expression of osteogenic growth factors such as bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (RUNX2), small mothers against decapentaplegic 1/5/8 (SMAD1/5/8), wingless-type MMTV integration site family member 3A (Wnt3a), and collagen type 1 (COL-1) via mitogen-activated protein kinase (MAPK) and serine/threonine protein kinase (Akt). Moreover, the RUNX2 activity of the taurine-treated group was enhanced by protein-protein interactions such as Wnt3a-induced p-AKT/RUNX2 and BMP-mediated SMADs/MAPK/RUNX2 interactions. Conclusion: Our in vitro and in vivo results suggested that taurine can be considered as a potential therapeutic candidate agent for preventing bone loss in postmenopausal osteoporosis.

Osteoporosis is induced by an imbalance between osteogenesis and bone resorption, and is treated with osteogenic drugs and/or resorption inhibitors. Resorption inhibitors, such as bisphosphonates, are orally used; however, orally active small molecules with osteogenic activity are not clinically available. We synthesized various types of small molecules and identified a series of diphenylamine and diphenylether derivatives that promoted osteoblast differentiation. Among them, diphenylether derivatives 13a, 13g, and 13h potently promoted osteoblast differentiation (EC 200 for increasing alkaline phosphatase activity = 11.3, 31.1, and 12.3 nM, respectively) and inhibited cyclin-dependent kinase 8 (CDK8) activity (IC 50  = 2.5, 7.8, and 3.9 nM, respectively), suggesting that their osteoblastgenic effects are mediated by the inhibition of CDK8. The ratio of the maximal plasma concentration after oral administration at 10 mg/kg in female rats and EC 200 for osteoblastogenesis was 148.1 for compound 13a, 53.4 for 13g, and 101.8 for 13h, indicating possible in vivo osteoblastogenic and osteogenic effects. In ovariectomized female rats, 13g and 13h at 10 mg/kg/d for 8 weeks increased plasma bone-type alkaline phosphatase activity, indicating enhanced in vivo osteoblastogenesis. Furthermore, micro-computed tomography (micro-CT) showed that both compounds increased femoral cortical bone volume and mineral contents, which were unaffected by ovariectomy, while having negligible effects on trabecular bone volume and mineral contents, which were markedly reduced by ovariectomy. In conclusion, diphenylamine and diphenylether structures are novel scaffolds for osteoblastogenesis enhancers via the inhibition of CDK8. Among them, 13g and 13h are candidates for anti-osteoporotic drugs with cortical bone-selective osteogenic effects.

Despite alternatives to autogenous bone graft for spinal fusion have been investigated, it has been shown that osteoconductive materials alone do not give a rate of fusion comparable with autogenous bone. This study analyzed a strontium substituted ß‐tricalcium phosphate (Sr‐ßTCP) associated with syngeneic, unexpanded, and undifferentiated mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ADSC) as a new tissue engineering approach for spinal fusion procedures. A posterolateral fusion was performed in 15 ovariectomized (OVX) and 15 sham‐operated (SHAM) Inbred rats. Both SHAM and OVX animals were divided into three groups: Sr‐ßTCP, Sr‐ßTCP + BMCSs, and Sr‐ßTCP + ADSCs. Animals were euthanized 8 weeks after surgery and the spines evaluated by manual palpation, micro‐CT, and histology. For both SHAM and OVX animals, the fusion tissue in the Sr‐ßTCP + BMSCs group was more solid. This effect was significantly higher in OVX animals by comparing the Sr‐ßTCP + BMCSs group with Sr‐ßTCP + ADSCs. Radiographical score, based on micro‐CT 2D image, highlighted that the Sr‐ßTCP + BMCSs group presented a similar fusion to Sr‐ßTCP and higher than Sr‐ßTCP + ADSCs in both SHAM and OVX animals. Micro‐CT 3D parameters did not show significant differences among groups. Histological score showed significantly higher fusion in Sr‐ßTCP + BMSCs group than Sr‐ßTCP and Sr‐ßTCP + ADSCs, for both SHAM and OVX animals. In conclusion, our results suggest that addition of BMSCs to a Sr‐ßTCP improve bone formation and fusion, both in osteoporotic and nonosteoporotic animal, whereas spinal fusion is not enhanced in rats treated with Sr‐ßTCP + ADSCs. Thus, for conducting cells therapy in spinal surgery BMSCs still seems to be a better choice compared with ADSCs. [ABSTRACT FROM AUTHOR]

Menopause is a risk factor for impaired glucose metabolism. Alternative treatment of estrogen for postmenopausal women is required. The present study was designed to investigate the effects of 5-week endurance running exercise (Ex) by treadmill on hyperglycemia and signal pathway components mediating glucose transport in ovariectomized (OVX) placebo-treated rats, compared with 4-week 17β-estradiol (E2) replacement or pair-feeding (PF) to the E2 group. Ex improved the hyperglycemia and insulin resistance index in OVX rats as much as E2 or PF did. However, Ex had no effect on body weight gain in the OVX rats. Moreover, Ex enhanced the levels of GLUT4 and phospho-TBC1D1 proteins in the gastrocnemius of the OVX rats, but E2 or PF did not. Instead, the E2 increased the Akt2/AS160 expression and activation in the OVX rats. This study suggests that endurance Ex training restored hyperglycemia through the TBC1D1/GLUT4 pathway in muscle by an alternative mechanism to E2 replacement. [ABSTRACT FROM AUTHOR]

Objective To observe the effect of secretin (SCT) on bone turnover biomarker and bone mineral density (BMD) in ovariectomized rats with osteoporosis. Methods A rat model of postmenopausal osteoporosis was prepared by bilateral ovarian removal. Sixty SD rats were randomly divided into sham operation group, control group, estrogen treatment group, and SCT treatment group, with 15 rats in each group. After 3 months of treatment, BMD of the lumbar vertebrae was measured. Serum procollagen I N-Terminal propeptide (PINP) and collagen type I C-terminal cross-linked telopeptide (CTX) were determined with ELISA. In addition, osteoporosis-related proteins were analyzed using a protein interaction network analysis tool (STRING 10.0). Results Compared with the sham operation group, the PINP levels in the model control group, the estrogen treatment group, and the secretin treatment group increased (P<0.05), and the CTX levels in the control group increased (P<0.05). BMD in the control group decreased (P<0.05). There was no significant difference in the levels of CTX and BMD between the estrogen-treated group and the SCT treatment group (P>0.05). Compared with the control group, the levels of PINP and CTX in the estrogen-treated group and the secretin treatment group decreased, while BMD increased (P<0.05). There was no significant difference in the levels of PINP, CTX, and BMD between the estrogen group and the SCT treatment group (P>0.05). Conclusion SCT improves the levels of PINP and CTX, increases BMD, and inhibits bone loss in osteoporosis ovariectomized rats. It has better anti-osteoporosis effect. [ABSTRACT FROM AUTHOR]

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