ObjectiveTo review the effects and mechanisms of various myokines secreted by skeletal muscle on various bone tissue cells.MethodsLiterature related to myokines and their regulation of bone tissue cells was reviewed and analyzed comprehensively in recent years.ResultsBone and skeletal muscle are important members of the motor system, and they are closely related in anatomy, genetics, and physiopathology. In recent years, it has been found that skeletal muscle can secrete a variety of myokines to regulate bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, and bone cells; these factors mutual crosstalk between myoskeletal unit, contact each other and influence each other, forming a complex myoskeletal micro-environment, and to some extent, it has a positive impact on bone repair and reconstruction.ConclusionMyokines are potential targets for the dynamic balance of bone tissue cells. In-depth study of its mechanism is helpful to the prevention and treatment of myoskeletal diseases.
Objective To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. Methods BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. Results The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. ConclusionVPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Objective To Investigate the effects of lithocholic acid (LCA) on the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods Twelve 10-week-old SPF C57BL/6J female mice were randomly divided into an experimental group (undergoing bilateral ovariectomy) and a control group (only removing the same volume of adipose tissue around the ovaries), with 6 mice in each group. The body mass was measured every week after operation. After 4 weeks post-surgery, the weight of mouse uterus was measured, femur specimens of the mice were taken for micro-CT scanning and three-dimensional reconstruction to analyze changes in bone mass. Tibia specimens were taken for HE staining to calculate the number and area of bone marrow adipocytes in the marrow cavity area. ELISA was used to detect the expression of bone turnover markers in the serum. Liver samples were subjected to real-time fluorescence quantitative PCR (RT-qPCR) to detect the expression of key genes related to bile acid metabolism, including cyp7a1, cyp7b1, cyp8b1, and cyp27a1. BMSCs were isolated by centrifugation from 2 C57BL/6J female mice (10-week-old). The third-generation cells were exposed to 0, 1, 10, and 100 μmol/L LCA, following which cell viability was evaluated using the cell counting kit 8 assay. Subsequently, alkaline phosphatase (ALP) staining and oil red O staining were conducted after 7 days of osteogenic and adipogenic induction. RT-qPCR was employed to analyze the expressions of osteogenic-related genes, namely ALP, Runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), as well as adipogenic-related genes including Adiponectin (Adipoq), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor γ (PPARγ). Results Compared with the control group, the body mass of the mice in the experimental group increased, the uterus atrophied, the bone mass decreased, the bone marrow fat expanded, and the bone metabolism showed a high bone turnover state. RT-qPCR showed that the expressions of cyp7a1, cyp8b1, and cyp27a1, which were related to the key enzymes of bile acid metabolism in the liver, decreased significantly (P<0.05), while the expression of cyp7b1 had no significant difference (P>0.05). Intervention with LCA at concentrations of 1, 10, and 100 μmol/L did not demonstrate any apparent toxic effects on BMSCs. Furthermore, LCA inhibited the expressions of osteogenic-related genes (ALP, Runx2, and OCN) in a dose-dependent manner, resulting in a reduction in ALP staining positive area. Concurrently, LCA promoted the expressions of adipogenic-related genes (Adipoq, FABP4, and PPARγ), and an increase in oil red O staining positive area. Conclusion After menopause, the metabolism of bile acids is altered, and secondary bile acid LCA interferes with the balance of osteogenic and adipogenic differentiation of BMSCs, thereby affecting bone remodelling.
ObjectiveTo explore the protective effects of sodium valproic acid (VPA) on oxidative stress injury of osteoblasts induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and its mechanism. Methods Osteoblasts were isolated from the skulls of 10 newborn Sprague Dawley rats and cultured by tissue block method, and the 1st generation cells were identified by alkaline phosphatase (ALP) and alizarin red staining. The 3rd generation osteoblasts were cultured with 2-18 μmol/L CCCP for 2-18 minutes, and cell counting kit 8 (CCK-8) was used to detect the cell survival rate. An appropriate inhibitory concentration and culture time were selected for the preparation of osteoblasts oxidative stress injury model based on half maximal concentration principle. The cells were cultured with 0.2- 2.0 mmol/mL VPA for 12-72 hours, and CCK-8 was used to detect cell activity, and appropriate concentration was selected for further treatment. The 3rd generation cells were randomly divided into 4 groups, including blank control group (normal cultured cells), CCCP group (the cells were cultured according to the selected appropriate CCCP concentration and culture time), VPA+CCCP group (the cells were pretreated according to the appropriate VAP concentration and culture time, and then cultured with CCCP), VPA+CCCP+ML385 group (the cells were pretreated with 10 μmol/L Nrf inhibitor ML385 for 2 hours before VPA treatment, and other treatments were the same as VPA+CCCP group). After the above treatment was complete, the cells of 4 groups were taken to detect oxidative stress indicators [reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA)], cell apoptosis rate, ALP/alizarin red staining, and the relative expressions of osteogenic related proteins [bone morphogenetic protein 2 (BMP-2), RUNX2], anti-apoptotic family protein (Bcl2), apoptotic core protein (Cleaved-Caspase-3, Bax), channel protein (Nrf2) by Western blot. Results The osteoblasts were successfully extracted. According to the results of CCK-8 assay, the oxidative stress injury model was established by 10 μmol/L CCCP cultured for 10 minutes and 0.8 mmol/mL VPA cultured for 24 hours was selected for subsequent experiments. Compared with blank control group, the activity and mineralization capacity of osteoblasts in CCCP group decreased, the contents of ROS and MDA increased, the activity of SOD decreased, and the apoptosis rate increased. Meanwhile, the relative expressions of BMP-2, RUNX2, and Bcl2 decreased, and the relative expressions of Cleaved-Caspase-3, Nrf2, and Bax increased. The differences were significant (P<0.05). After further VPA treatment, the oxidative stress damage of osteoblasts in VPA+CCCP group was relieved, and the above indexes showed a recovery trend (P<0.05). In VPA+CCCP+ML385 group, the above indexes showed an opposite trend (P<0.05), and the protective effects of VPA were reversed. Conclusion VPA can inhibit the CCCP-induced oxidative stress injury of osteoblasts and promote osteogenesis via Keap1/Nrf2/Are pathway.
Objective To investigate the effect of collagen peptides from walleye pollock skin on the microstructure of osteoporosis model in ovariectomized rats, and to explore the feasibility of preventing and treating oste- oporosis. Methods Sixty adult Wistar female rats, weighing (250±10) g, were randomly divided into 5 groups (12 rats each group): normal group (group A), osteoporosis model group (group B), osteoporosis model+collagen peptides from walleye pollock skin prevention group (group C), osteoporosis model+low concentration of collagen peptides from walleye pollock skin treatment group (group D), and osteoporosis model+high concentration of collagen peptides from walleye pollock skin treatment group (group E). The rats in groups B, C, D, and E were removed bilateral ovarian to establish osteoporosis model. The rats in group C were treated with stomach perfusion of the collagen peptides from walleye pollock skin (1.0 g/kg) from 4 weeks after operation for 6 weeks; and the rats in groups D and E were treated with stomach perfusion of the collagen peptides from walleye pollock skin (0.5, 1.0 g/kg respectively) at 6 weeks after operation for 6 weeks. The rats in groups A and B were given equal volume of normal saline at the same time after operation. At 24 hours after the last administration, the femoral gray value of rats in groups A and B were measured by X-ray film; HE staining was performed on the proximal tibial bone of the left side in 4 groups; the histopathological changes of the bone were observed and the trabecular number (TN), mean trabecular plate thickness (MTPT), mean trabecular plate spacing (MTPS), trabecular bone volume (TBV), mean bone cortical thickness (MBCT) were measured; immunohistochemical staining was performed to observe the expression levels of caltitonin receptor (CTR) and interleukin 1 (IL-1). Results The femoral gray value of group B was significantly lower than that of group A (t=45.130, P=0.000), which indicated that the ovariectomized rat model was successfully prepared. Histological observation showed that TN, MTPS, TBV, and MBCT in groups A, C, and E were significantly different from those in group B (P<0.05). The histological parameters of bone tissue in group C were significantly different from those in groups D and E (P<0.05). TN, MTPS, TBV, and MBCT in group D were significantly different from those in group A (P<0.05); only MTPS in group E was significantly different from that in group A (P<0.05). MTPS, TBV, and MBCT in group E were significantly different from those in group D (P<0.05). The immunohistochemical staining showed that the levels of CTR and IL-1 in groups A, C, D, and E were lower than those in group B, in groups C and E were lower than in group D, showing significant differences (P<0.05). Conclusion Collagen peptides from walleye pollock skin can improve the bone microstructure of osteoporotic rats, and its mechanism may be related to the inhibition of CTR and IL-1 expression in bone tissue, but it has not been found to prevent osteoporosis.
Objective To explore the potential causal relationship between thyroid dysfunction and osteoporosis (OP) through bidirectional two-sample Mendelian randomization (MR) analysis to provide genetic evidence for the risk association between thyroid dysfunction and OP, and provide reference for early prevention and treatment of OP. Methods Causal relationships were estimated based on data from genome-wide association studies for hypothyroidism (n=410141), hyperthyroidism (n=460499), Hashimoto thyroiditis (n=395640), and OP (n=212778). The inverse variance weighted method was used as the main analysis method, and the other four methods were used as the supplementary analysis methods to evaluate the causal effect of thyroid dysfunction and OP. Results The results of inverse variance weighted method showed that hypothyroidism [odds ratio (OR)=1.097, 95% confidence interval (CI) (1.017, 1.183), P=0.017], hyperthyroidism [OR=1.089, 95%CI (1.000, 1.186), P=0.049] and Hashimoto thyroiditis [OR=1.190, 95%CI (1.054, 1.343), P=0.005] were positively correlated with the causal effect of OP. The results of reverse MR analysis did not support that OP would increase the risk of hypothyroidism, hyperthyroidism or Hashimoto thyroiditis (P>0.05). In the bidirectional MR analyses, there was no heterogeneity in Cochran Q detection, MR-Egger intercept test results showed that there was no horizontal pleotropy, and the leave-one-out method analysis results showed that the MR analysis results were reliable. Conclusion Hypothyroidism, hyperthyroidism, and Hashimoto thyroiditis increase the risk of OP, while OP is not found to increase the risk of thyroid dysfunction in reverse studies.
Objective To explore the correlation of risk factors affecting the L2-4BMD level in patients with post-menopausal osteoporosis. Methods Ninety-two patients with post-menopausal osteoporosis were surveyed with a retrospective questionnaire. We used the findings to set up a multiple stepwise regression model and perform correlation analysis with L2-4BMD levels as the dependent variable and risk factors as the independent variables. Results Assuming that age has a definite effect on the L2-4BMD level of menopausal women, menopausal age limit, history of milk drinking, menopausal age, menarche age, fracture history and bend-back entered into the multiple stepwise regression equation. Conclusions Menopausal age limit, history of milk drinking, menopausal age, menarche age, fracture history, and bend-back influence patients with menopausal osteoporosis.The menopausal age limit is especially important. Awareness of the risk factors of osteoporosis should be raised.
Objective To evaluate the effectiveness of hormone replacement therapy (HRT) for osteoporosis in postmenopausal women. Method Systematic reviews and meta-analyses were searched in Cochrane Library (Issue 4, 2008), MEDLINE (1978-2008) and Clinical Evidence database. Search terms included Postmenopausal (post-menopausal) osteoporosis, therapy, vertebral fracture, hormone replacement therapy, randomized controlled trial, meta analysis, female,human. Result A total of 4 protocols were found in Cochrane Library and a meta-analyse was found in MEDLINE. The result demonstrated that both cancellous and cortical bone mineral density increased after HRT. Statistically significant reductions in the risk of vertebral and non-vertebral fracture were also found. Conclusion HRT can reduce the risk of osteoporotic fracture by increasing bone density. However, other disease and adverse event were also associated with the BMD increase. Therefore, both advantage and disadvantage should be considered before applying HRT therapy to postmenopausal osteoporosis patients.
ObjectiveTo discuss the effectiveness of osteoporosis therapy apparatus combined with calcium carbonate D3 tablets (Caltrate D) for the treatment of senile osteoporosis. MethodFrom March 2013 to March 2014, 110 patients with senile osteoporosis were selected and randomly divided into study group (n=63) and control group (n=47). Patients in the study group were given 600 mg calcium carbonate D3 tablet combined with osteoporosis therapy apparatus treatment for 30 minutes per day. Meanwhile, patients in the control group were given 600 mg calcium carbonate D3 tablet every day. The treatment course of both groups of patients lasted for 6 months. The change of bone pain and bone mineral density (BMD) were compared and analyzed after the treatment. ResultsThe effective rate of pain relieving in the study group and control group was 92.07% and 85.11%, respectively after 6 months; the difference was not significant (χ2=1.341, P=0.247). BMD was improved in both groups, but BMD increased more in the study group[(0.327±0.107)g/cm2] than in the control group[(0.237±0.115)g/cm2] with statistical significance (P<0. 05). ConclusionsOsteoporosis therapy apparatus combined with calcium carbonate D3 is an effective method for the treatment of senile osteoporosis.
With the aging of the population, the incidence of benign paroxysmal positional vertigo (BPPV) and osteoporosis have been increasing year by year, and the incidence of BPPV in vertigo related diseases has also been ranked first. There are similarities in structure, formation and metabolic mechanism between bone and otolith, but there is no consistent conclusion on the relationship between BPPV and osteoporosis. This article summarizes the current situation of the research on the correlation between BPPV and osteoporosis, the common risk factors and the related co-occurring mechanisms, aiming to provide more ideas for the prevention and treatment of BPPV patients, and improve the prevention and treatment ability of the co-diseases in the elderly.