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Zhongguo Xiu Fu Chong Jian Wai Ke Za... Jan 2024To Investigate the effects of lithocholic acid (LCA) on the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).
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 ( <0.05), while the expression of cyp7b1 had no significant difference ( >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.
Topics: Female; Mice; Animals; Core Binding Factor Alpha 1 Subunit; PPAR gamma; Steroid 12-alpha-Hydroxylase; Mice, Inbred C57BL; Cell Differentiation; Osteogenesis; Mesenchymal Stem Cells; Bile Acids and Salts; Bone Marrow Cells; Cells, Cultured; Azo Compounds
PubMed: 38225846
DOI: 10.7507/1002-1892.202308050 -
American Journal of Physiology. Cell... Mar 2024The phosphodiesterase enzymes mediate calcium-phosphate deposition in various tissues, although which enzymes are active in bone mineralization is unclear. Using gene...
The phosphodiesterase enzymes mediate calcium-phosphate deposition in various tissues, although which enzymes are active in bone mineralization is unclear. Using gene array analysis, we found that a member of ecto-nucleotide pyrophosphatase/phosphodiesterase family, ENPP2, was strongly down-regulated with age in stromal stem cells that produce osteoblasts and make bone. This is in keeping with reduced bone formation in older animals. Thus, we hypothesized that ENPP2 is, at least in part, an early mediator of bone formation and thus may reflect reduced bone formation with age. Since ENPP2 has not previously been shown to have a role in osteoblast differentiation, we studied its effect on bone differentiation from stromal stem cells, verified by flow cytometry for stem cell antigens. In these remarkably uniform osteoblast precursors, we did transfection with ENPP2 DsiRNA, scrambled DsiRNA, or no transfection to make cells with normal or greatly reduced ENPP2 and analyzed osteoblast differentiation and mineralization. Osteoblast differentiation down-regulation was shown by alizarin red binding, silver staining, and alkaline phosphatase activity. Differences were confirmed by real-time PCR for alkaline phosphatase (ALPL), osteocalcin (BGLAP), and ENPP2 and by Western Blot for Enpp2. These were decreased, ∼50%, in osteoblasts transfected with ENPP2 DsiRNA compared with cells transfected with a scrambled DsiRNA or not transfected (control) cells. This finding is the first evidence for the role of ENPP2 in osteoblast differentiation and mineralization. We report the discovery that the ecto-nucleotide pyrophosphatase/phosphodiesterase, ENPP2, is an important regulator of early differentiation of bone-forming osteoblasts.
Topics: Animals; Osteogenesis; Alkaline Phosphatase; Cell Differentiation; Phosphoric Diester Hydrolases; Calcinosis; Pyrophosphatases
PubMed: 38223929
DOI: 10.1152/ajpcell.00692.2023 -
Medicine Jan 2024Magnetic therapy may have some potential in treating osteoporosis, and this meta-analysis aims to study the efficacy of magnetic therapy for osteoporotic patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Magnetic therapy may have some potential in treating osteoporosis, and this meta-analysis aims to study the efficacy of magnetic therapy for osteoporotic patients.
METHODS
We have searched several databases including PubMed, EMbase, Web of Science, EBSCO and Cochrane library databases, and selected the randomized controlled trials comparing the efficacy of magnetic therapy for osteoporotic patients. This meta-analysis was conducted using the random-effect or fixed-effect model based on the heterogeneity.
RESULTS
Five randomized controlled trials were included in this meta-analysis. Compared with sham procedure in osteoporotic patients, magnetic therapy was associated with significantly increased bone mineral density (standard mean difference [SMD] = 2.39; 95% confidence interval [CI] = 0.27-4.51; P = .03), decreased pain scores (mean difference [MD] = -0.86; 95% CI = -1.04 to -0.67; P < .00001), and calcium (MD = -0.61; 95% CI = -0.92 to -0.29; P = .0002), but revealed no influence on phosphate (MD = 0.07; 95% CI = -0.30 to 0.44; P = .71), osteocalcin (SMD = 0.65; 95% CI = -2.87 to 4.17; P = .72), or ALP (SMD = -0.43; 95% CI = -0.92 to 0.07; P = .09).
CONCLUSIONS
Magnetic therapy may be effective for the treatment of osteoporotic patients.
Topics: Humans; Osteoporosis; Magnetic Phenomena
PubMed: 38215089
DOI: 10.1097/MD.0000000000036881 -
Nanomaterials (Basel, Switzerland) Dec 2023Maxillofacial bone defects are treated by autografting or filling with synthetic materials in various forms and shapes. Electrospun nanobiomaterials are becoming popular...
In Vivo Evaluation of Bone Regenerative Capacity of the Novel Nanobiomaterial: β-Tricalcium Phosphate Polylactic Acid-co-Glycolide (β-TCP/PLLA/PGA) for Use in Maxillofacial Bone Defects.
Maxillofacial bone defects are treated by autografting or filling with synthetic materials in various forms and shapes. Electrospun nanobiomaterials are becoming popular due to their easy placement and handling; combining ideal biomaterials extrapolates better outcomes. We used a novel electrospun cotton-like fiber made from two time-tested bioresorbable materials, β-TCP and PLLA/PGA, to check the feasibility of its application to maxillofacial bone defects through an in vivo rat mandibular bone defect model. Novel β-TCP/PLLA/PGA and pure β-TCP blocks were evaluated for new bone regeneration through assessment of bone volume, inner defect diameter reduction, and bone mineral density. Bioactive/osteoconductivity was checked by scoring the levels of Runt-related transcription factor x, Leptin Receptor, Osteocalcin, and Periostin biomarkers. Bone regeneration in both β-TCP/PLLA/PGA and β-TCP was comparable at initial timepoints. Osteogenic cell accumulation was greater in β-TCP/PLLA/PGA than in β-TCP at initial as well as late phases. Periostin expression was more marked in β-TCP/PLLA/PGA. This study demonstrated comparable results between β-TCP/PLLA/PGA and β-TCP in terms of bone regeneration and bioactivity, even with a small material volume of β-TCP/PLLA/PGA and a decreased percentage of β-TCP. Electrospun β-TCP/PLLA/PGA is an ideal nanobiomaterial for inducing bone regeneration through osteoconductivity and bioresorbability in bony defects of the maxillofacial region.
PubMed: 38202548
DOI: 10.3390/nano14010091 -
BMC Musculoskeletal Disorders Jan 2024Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying...
BACKGROUND
Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying mechanism and bring a potential preventive strategy for postmenopausal osteoporosis in the future.
METHODS
An ovariectomy (OVX)-induced rat osteoporosis model was established for in vivo experiments. Micro-computed tomography and three-point bending test were used to evaluate bone strength. Histological femur slices were processed for immunohistochemistry (IHC). Bone turnover markers and nitric oxide (NO) concentrations in serum were determined with enzyme-linked immunosorbent assay (ELISA). The mouse embryo osteoblast precursor (MC3T3-E1) cells were used for in vitro experiments. The cell viability was analysed with a Cell Counting Kit‑8. We performed Alizarin Red S staining and alkaline phosphatase (ALP) activity assay to observe the differentiation status of osteoblasts. Western blotting was adopted to detect the expression of osteogenesis related proteins and AMP-activated protein kinase/endothelial nitric oxide synthase (AMPK/eNOS) in osteoblasts. DAF-FM diacetate was used for semi-quantitation of intracellular NO.
RESULTS
In OVX rats, alamandine alleviated osteoporosis and maintained bone strength. The IHC showed alamandine increased osteocalcin and collagen type I α1 (COL1A1) expression. The ELISA revealed alamandine decreased bone turnover markers and restored NO level in serum. In MC3T3-E1 cells, alamandine promoted osteogenic differentiation. Western blotting demonstrated that alamandine upregulated the expression of osteopontin, Runt-related transcription factor 2 and COL1A1. The intracellular NO was also raised by alamandine. Additionally, the activation of AMPK/eNOS axis mediated the effects of alamandine on MC3T3-E1 cells and bone tissue. PD123319 and dorsomorphin could repress the regulating effect of alamandine on bone metabolism.
CONCLUSION
Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.
Topics: Mice; Female; Animals; Rats; Osteogenesis; AMP-Activated Protein Kinases; Nitric Oxide Synthase Type III; X-Ray Microtomography; Osteoporosis; Oligopeptides
PubMed: 38200474
DOI: 10.1186/s12891-023-07159-2 -
Frontiers in Medicine 2023In traditional Chinese medicine, Jintiange capsules are frequently used to treat metabolic bone diseases and strengthen bones and tendons. The main component of...
Efficacy of the Chinese herbal medicine Jintiange capsules in the postoperative treatment of osteoporotic vertebral compression fractures: a systematic review and meta-analysis.
BACKGROUND
In traditional Chinese medicine, Jintiange capsules are frequently used to treat metabolic bone diseases and strengthen bones and tendons. The main component of Jintiange capsules is bionic tiger bone powder. However, the active ingredients and proteins are derived from other animal bones, with chemical profiles similar to that of natural tiger bone. This study aimed to explore the efficacy of Jintiange capsules, a Chinese herbal medicine, in the postoperative treatment of osteoporotic vertebral compression fractures (OVCFs).
METHODS
In this systematic review, literature was retrieved using PubMed, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Web of Science, the Wanfang Database, the Chinese Biomedical Literature Database, and the Chinese VIP Database from inception to July 2023. The primary outcome measures were the bone mineral density (BMD) and effective rate. The secondary outcome measures were the visual analog pain score (VAS), Oswestry disability index (ODI), Cobb's angle, serum osteocalcin, serum alkaline phosphatase, and adverse events. RevMan 5.4 and STATA 17.0 software were used for data analysis.
RESULTS
We enrolled randomized controlled trials (RCTs) focusing on 1,642 patients in the meta-analysis. The meta-analysis illustrated that Jintiange capsules significantly increased the BMD of the lumbar spine ( < 0.00001), femoral neck ( = 0.0005), and whole body ( = 0.01). The subgroup analysis of Jintiange capsules combination therapy showed that the BMD of the lumbar spine and whole body was significantly improved with Jintiange capsules ( < 0.00001). The test for the overall effect showed that Jintiange capsules had a significantly higher effective rate than the control groups ( = 0.003). Additionally, the overall effect test showed that Jintiange capsules decreased the VAS and ODI ( < 0.00001) and Cobb's angle ( = 0.02), and improved serum OC and ALP ( < 0.00001) compared with the controls. Furthermore, the pooled analysis of adverse reactions showed no serious impacts on the treatment of OVCFs.
CONCLUSION
Jintiange capsules demonstrate high safety and efficacy in the treatment of OVCFs, including increasing BMD, the lift effect rate, serum OC levels, and pain relief, decreasing the ODI, serum ALP levels, and adverse events, and improving Cobb's angle. Additional research is required to validate the efficacy of Jintiange capsules for the postoperative treatment of OVCFs.: https://www.crd.york.ac.uk/PROSPERO.
PubMed: 38162884
DOI: 10.3389/fmed.2023.1289818 -
Metabolites Dec 2023Reduced expression of the plasma membrane citrate transporter , also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and...
Reduced expression of the plasma membrane citrate transporter , also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and metabolic diseases. Citrate, a vital component of the tricarboxylic acid cycle, constitutes 1-5% of bone weight, binding to mineral apatite surfaces. Our previous research highlighted osteoblasts' specialized metabolic pathway facilitated by regulating citrate uptake, production, and deposition within bones. Disrupting this pathway impairs bone mineralization in young mice. New Mendelian randomization analysis using UK Biobank data indicated that SNPs linked to reduced function lowered osteoporosis risk. Comparative studies of young (10 weeks) and middle-aged (52 weeks) osteocalcin-cre-driven osteoblast-specific knockout mice () showed a sexual dimorphism: while middle-aged females exhibited improved elasticity, middle-aged males demonstrated enhanced bone strength due to reduced function. These findings suggest reduced function could attenuate age-related bone fragility, advocating for inhibition as a potential osteoporosis treatment.
PubMed: 38132868
DOI: 10.3390/metabo13121186 -
PloS One 2023The aim of this study was to compare the ability of demineralized (DMB) and decellularized (DCC) bovine bone granules to support bone regeneration in rat calvaria...
The aim of this study was to compare the ability of demineralized (DMB) and decellularized (DCC) bovine bone granules to support bone regeneration in rat calvaria critical-size defects. DMB and DCC were prepared using a previously published method. The granule size used ranged between 500 and 750 μm. A total of forty-eight Sprague-Dawley rats were divided into two groups (n = 24). A pair of 5 mm diameter defects were created on the calvaria of the rats in the right and left parietal bone in both groups. Group A animals received DMB granules and Group B received DCC granules in the right parietal defect side while the left parietal untreated defect acted as sham surgery for both groups. Four animals per group were euthanized in a CO2 chamber at day 7, 14 and 21 post-surgery and the calvaria implantation site biopsy harvested was subjected to osteogenic gene expression analysis. Another four animals per group were euthanized at days 15, 30 and 60 post surgery and the calvaria implantation site biopsy harvested was subjected to histological, immunohistochemistry, RAMAN spectroscopy and Micro-CT analysis at the mentioned time points. Statistical analysis was conducted using t-tests and ANOVA. Histomorphometry showed significantly higher new bone formation in the DCC sites (p<0.05) compared to DMB. Both DMB and DCC implantation sites showed distinct staining for osteocalcin and osteopontin proteins compared to their respective sham sites. By day 21 after implantation, DCC sites demonstrated significantly elevated mRNA levels of osteonectin (p<0.001), osteopontin (p<0.001), osteocalcin (p<0.0001), ALP (p<0.01), and BMP-2 (p<0.001) compared to DMB. However, VEGF expression showed no significant differences at this time point between the two groups. Micro-CT analysis also showed enhanced defect closure and higher bone density in DCC implanted sites while RAMAN spectra demonstrated increased abundance of collagen and bone minerals, especially, PO43- ions than DMB. In conclusion, both DMB and DCC granules demonstrated favorable osteogenic potential in critical-sized defects, with DCC exhibited superior osteoconductive, osteoinductive and osteogenesis properties.
Topics: Rats; Animals; Cattle; Osteogenesis; Rats, Sprague-Dawley; Osteopontin; Osteocalcin; Skull; Bone Regeneration; Minerals
PubMed: 38127838
DOI: 10.1371/journal.pone.0294291 -
Frontiers in Endocrinology 2023Weight reduction often accompanies muscle loss. Existing studies highlight the involvement of osteocalcin (OC) in energy metabolism and its potential to prevent... (Observational Study)
Observational Study
OBJECTIVE
Weight reduction often accompanies muscle loss. Existing studies highlight the involvement of osteocalcin (OC) in energy metabolism and its potential to prevent age-related muscle loss. Nevertheless, these studies predominantly involve individuals with hyperglycemia, yielding conflicting research outcomes. This study investigated the protective role of OC against muscle loss during weight reduction in individuals without metabolic syndrome (MetS).
MEASURES
We enrolled 130 overweight or obese individuals without MetS in a 4-month high-protein, energy-restricted dietary weight management program conducted at two clinic centers. Body composition and laboratory tests were assessed both before and after weight loss. Correlation and regression analysis were made between the changes in metabolic indicators and muscle mass during weight loss.
RESULTS
Following weight loss, there was a decrease in body mass index (BMI), percentage of body fat (PBF), visceral fat area (VFA), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), and lipid profile, and increase in the percentage of skeletal muscle (PSM) and vitamin D. There was no change in osteocalcin (OC) during the intervention. Correlation analysis of the relative changes in all metabolic indicators revealed a positive correlation between OC and PSM (r=0.383, p=0.002). Multiple linear regression analysis found that OC has a significant protective effect on muscles during weight loss in males after adjusting for confounding factors (β=0.089, p=0.017).
CONCLUSION
High-protein, energy-restricted diets demonstrate efficacy in enhancing metabolic indicators within the weight-loss population. Furthermore, OC exhibits a protective effect on muscle mass during weight reduction in individuals without MetS, with this effect being particularly evident in males.
Topics: Humans; Male; Metabolic Syndrome; Muscle, Skeletal; Osteocalcin; Prospective Studies; Weight Loss
PubMed: 38093960
DOI: 10.3389/fendo.2023.1308452 -
Journal of the Endocrine Society Dec 2023Patients with primary (PAI) and secondary adrenal insufficiency (SAI) experience bone metabolism alterations, possibly due to excessive replacement. Dual-release...
CONTEXT
Patients with primary (PAI) and secondary adrenal insufficiency (SAI) experience bone metabolism alterations, possibly due to excessive replacement. Dual-release hydrocortisone (DR-HC) has shown promising effects on several parameters, but bone metabolism has seldom been investigated.
OBJECTIVE
We evaluated the long-term effects of once-daily DR-HC on bone in PAI and SAI.
METHODS
Patients on immediate-release glucocorticoid therapy were evaluated before and up to 6 years (range, 4-6) after switching to equivalent doses of DR-HC, yielding data on bone turnover markers, femoral and lumbar spine bone mineral density (BMD), and trabecular bone score (TBS).
RESULTS
Thirty-two patients (19 PAI, 18 female), median age 52 years (39.4-60.7), were included. At baseline, osteopenia was observed in 38% of patients and osteoporosis in 9%, while TBS was at least partially degraded in 41.4%. Higher body surface area-adjusted glucocorticoid doses predicted worse neck ( < .001) and total hip BMD ( < .001). Longitudinal analysis showed no significant change in BMD. TBS showed a trend toward decrease ( = .090). Bone markers were stable, albeit osteocalcin levels significantly varied. PAI and SAI subgroups behaved similarly, as did patients switching from hydrocortisone or cortisone acetate. Compared with men, women exhibited worse decline in TBS ( = .017) and a similar trend for neck BMD ( = .053).
CONCLUSION
After 6 years of chronic DR-HC replacement, BMD and bone markers remained stable. TBS decline is more likely due to an age-related derangement of bone microarchitecture rather than a glucocorticoid effect. Our data confirm the safety of DR-HC replacement on bone health in both PAI and SAI patients.
PubMed: 38090230
DOI: 10.1210/jendso/bvad151