Naringenin prevents osteoblast senescence in d-galactose-induced aging conditions via estrogen receptor-mediated pathway.

The objective of this in vitro study was to examine the impact of metformin (MET) at different concentrations (0.1, 1, 10, 50, and 100 mM) on rat primary osteoblasts, as the results obtained so far are inconsistent. Osteoblast apoptosis, viability, alkaline phosphatase (ALPL) activity, production of osteoblast-specific biomarkers, including ALPL, osteocalcin (BGLAP), type I collagen alpha 1 (COL1A1), integrin-binding sialoprotein (IBSP), bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor (VEGF), tumor necrosis factor ligand superfamily member 11 (TNFSF11 or RANKL), as well as calcium/collagen deposition were assessed. Our results revealed that a dose of 100 mM was cytotoxic to osteoblasts and resulted in a complete loss of their viability. Therefore, this concentration was excluded from further analyses. In general, MET exhibited a dose-dependent impact on multiple osteoblast-specific functional biomarkers, with beneficial effects noted on ALPL activity (at 0.1 and 1 mM) as well as on the levels of ALPL (0.1 and 1 mM), BGLAP (at 0.1-50 mM), IBSP (at 0.1-50 mM), BMP2 (at 0.1, 10 and 50 mM), VEGF (at 0.1 and 1 mM), and RANKL (at 0.1 mM). Calcium/collagen deposition at concentrations of 0.1 and 1 mM reached the same level as control cells, higher doses (10 and 50 mM) dramatically reduced cell viability after 21 days and the aforementioned parameters could not be evaluated. It can be concluded that MET at concentrations up to 1 mM can promote osteoblast viability, osteogenic differentiation, angiogenic signaling, and reduce osteoclastogenesis. Key words Metformin " Osteoblasts " Bone health " In vitro.

Naringin-loaded metal-organic framework biomimetic hydrogel system mitigates wear particle-induced periprosthetic osteolysis by suppressing aseptic inflammation and osteoblast apoptosis

To elucidate the role and mechanism of HOXA7 in osteoporosis (OP), with the goal of informing future research directions in OP. We assessed HOXA7 gene and protein expression; the effect of HOXA7 on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs); and proliferation, apoptosis, and autophagy in MC3T3-E1 cells. We also evaluated p38 MAPK/JNK pathway-associated proteins in hBMSCs and MC3T3-E1 cells. Cells were transfected with si-HOXA7 and cultured with or without the JNK inhibitor SP600125 or the p38 inhibitor SB203580, after which cell viability, apoptosis, and autophagy were re-assessed. HOXA7 overexpression inhibited osteogenic differentiation of hBMSCs, reduced OPG, OPN, and RUNX2 expression in hBMSCs, and decreased proliferation while promoting apoptosis in MC3T3-E1 cells. In vitro, HOXA7 modulated autophagy markers in MC3T3-E1 cells. Phosphorylated JNK and p38 (p-JNK, p-p38) were increased in hBMSCs following osteogenic induction, whereas HOXA7 upregulation significantly suppressed p-JNK and p-p38 in MC3T3-E1 cells. SP600125 and SB203580 attenuated the effects of HOXA7 silencing on proliferation, apoptosis, and autophagy in MC3T3-E1 cells. HOXA7 reduces osteogenesis and osteoblast proliferation and promotes osteoblast apoptosis via the p38 MAPK/JNK pathway, suggesting potential therapeutic avenues against OP.

This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board. This follows the receipt of a notification from a reader, alerting the Editorial Board to irregularities in the flow cytometry graphs, some of which suggest that the graphs could have been hand-drawn. The authors were contacted regarding the concerns and the retraction but have not yet responded or provided requested raw data. Given the extent of the issues raised, the Editorial Board stand by the decision to retract the article.

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, characterized by severe impairment of osteoblast function and increased bone fragility. Current therapeutic options inadequately address glucocorticoid (GC)-induced osteoblast apoptosis and suppress osteogenesis, highlighting the need for novel targeted interventions. To explore the molecular pathogenesis of GIOP and identify therapeutic targets, we performed integrated transcriptomic analysis, bioinformatics approaches, and multiple experimental validation methods. We demonstrate that dexamethasone (DEX), a prototypical GC, robustly upregulates osteoglycin (OGN) expression in both cellular and animal models. Crucially, the transcription factor ELF5 functions as a critical transcriptional repressor of OGN, counteracting DEX effects. ELF5-mediated OGN repression is essential for maintaining pro-survival PI3K/AKT/mTOR signaling integrity in osteoblasts. Molecular docking confirmed stable, high-affinity binding between the natural compound chrysophanol and OGN. Functionally, chrysophanol effectively antagonized DEX-induced OGN elevation and mitigated osteoblast apoptosis. This work is the first to define a role for the DEX-OGN-ELF5 axis in PI3K/AKT/mTOR signaling as critical for osteoblast survival in GIOP. Chrysophanol, as a novel natural compound targeting this OGN-centric axis, presents a promising and potentially safer therapeutic alternative to bisphosphonates, which are associated with risks like atypical femoral fractures and osteonecrosis of the jaw. Our findings offer novel insights into the molecular pathogenesis of GIOP, identify a potential druggable ELF5/OGN/PI3K/AKT/mTOR signaling axis, and establish a basis for future translational research in GC-induced bone diseases.

Introduction Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive and debilitating disorder caused by excessive glucocorticoid exposure. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) and their exosome (Exos)-mediated signal transduction plays a key role in SONFH; however, the exact pathways involved remain under active investigation. Methods The differential expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) related to the Exos-mediated pathway in Exos derived from human BMSCs (hBMSCs) of patients with SONFH and control patients were analyzed by next-generation sequencing (NGS). The miR‐199a‐3p was identified as a differentially expressed miRNA, and its expression in BMSCs and their corresponding Exos was subsequently validated using quantitative real-time polymerase chain reaction. A series of functional experiments then confirmed that miR-199a-3p modulated osteoblasts (OBs) and human umbilical vein endothelial cells (HUVECs) activities via the Exos-mediated pathway, including cell proliferation, apoptosis, osteogenesis, and angiogenesis, with or without exposure to high-dose dexamethasone (Dex). Results NGS results revealed a total of 6,953 differentially expressed ncRNAs, 260 differentially expressed miRNAs, 13,577 differentially expressed mRNAs were identified in hBMSCs from patients with SONFH compared to controls. In hBMSCs-Exos, 207 differentially expressed ncRNAs, 183 differentially expressed miRNAs, and 1,075 differentially expressed mRNAs were detected. Integrated analysis of transcripts expressed in both hBMSCs and hBMSCs-Exos identified 659 differentially expressed ncRNAs, 11 differentially expressed miRNAs, and 1,600 differentially expressed mRNAs. The results of bioinformatics analysis showed that these differentially expressed RNAs were involved in regulation of endocytosis, receptor-mediated endocytosis, response to extracellular stimuli, and bone mineralization. Furthermore, the validation results demonstrated that the suppression of miR-199a-3p promoted proliferation, osteogenesis, and angiogenesis, while inhibiting apoptosis of OBs and HUVECs activities and exposed to high-dose Dex. Discussion This study identified differential expression profiles of ncRNAs, miRNAs and mRNAs related to the Exos-mediated pathway in SONFH through integrated analysis, and further demonstrated the negative role of miR‐199a‐3p in SONFH, involving proliferation, osteogenesis, and angiogenesis, as well as the regulation of apoptosis of OBs and HUVECs exposed to high-dose Dex through the hBMSCs-Exos-mediated pathway. Therefore, targeting miR‐199a‐3p may enhance the therapeutic efficacy of Exos-based treatments for SONFH.

Chronic stress and sustained hypothalamic-pituitary-adrenal (HPA) axis activation are major contributors to metabolic bone diseases, including osteoporosis. However, the precise molecular mechanisms by which chronic stress-induced HPA axis dysregulation drives bone deterioration remain unclear. A Chronic Unpredictable Mild Stress (CUMS) model was established in male rats to simulate prolonged stress exposure. Animals were randomly allocated into three groups: control, 10-week CUMS, and 20-week CUMS (n = 10/group). Model validity was confirmed via behavioral assessments. Bone mineral density (BMD) and trabecular microarchitecture were quantified using micro-computed tomography (micro-CT). Serum corticosterone (CORT) levels, HPA axis negative feedback function, and the expression of pro-inflammatory cytokines (IL-1β, TNF-α) in HPA-regulatory brain regions (hippocampus, prefrontal cortex, hypothalamus) were assessed. Critically, glucocorticoid receptor (GR) expression and nuclear translocation in these brain regions and bone tissue were examined by immunofluorescence and Western blot analysis. CUMS exposure induced progressive, time-dependent bone loss, with the 20-week group exhibiting significantly greater reductions in BMD and trabecular quality compared to the 10-week and control groups. While the HPA axis showed initial hyperactivation, the 20-week group displayed adrenal exhaustion (reduced serum CORT) alongside elevated ACTH, indicating feedback failure. Mechanistically, stress significantly impaired GR nuclear translocation in both brain and bone tissues, coinciding with the upregulation of FKBP5 and pro-inflammatory cytokines. Notably, despite low systemic CORT at late stages, skeletal 11β-HSD1 expression was significantly upregulated, creating a local microenvironment of glucocorticoid toxicity that aggravated osteoblast apoptosis. Our findings demonstrate that chronic stress induces progressive, time-dependent bone loss through a cascade of HPA axis dysregulation and impaired GR signaling. The FKBP5-mediated impairment of GR nuclear translocation in both central and peripheral tissues fosters glucocorticoid resistance, perpetuating hypercortisolemia and a pro-inflammatory milieu that directly accelerates osteoblast apoptosis and bone deterioration. These findings identify the HPA-GR axis as a critical pathway linking chronic stress to osteoporosis and suggest that restoring GR signaling offers a potential therapeutic strategy.

Objectives: We evaluated the effect of diacerein, an anti-inflammatory drug, on the activity and survival of alveolar bone osteoblasts in rats with periodontitis. Methods: The rats with periodontitis received diacerein (PDG) or saline solution (PSG) for 7, 15 and 30 days. In gingiva samples, Nfkb1 and Bmp2 gene expressions were evaluated, and maxillae were processed for light and transmission electron microscopy. Results: In PDG, the tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) immunoexpression decreased in parallel with the increase in alkaline phosphatase (ALP) and bone area over time. At 15 and 30 days, Nfkb1 expression decreased in PDG compared to PSG, whereas at 30 days, the Bmp2 expression was greater in PDG than in PSG. Immunofluorescence for IL-10, an anti-inflammatory cytokine, was greater in PDG than in PSG at 15 and 30 days. In PSG, the significant increase in the number of TUNEL-positive osteoblasts was accompanied by the presence of osteoblasts with condensed chromatin nuclei or caspase-3-immunolabelled osteoblasts. In contrast, the number of TUNEL-positive osteoblasts was significantly lower in PDG than in PSG specimens at all time points. Conclusions: Therefore, the diacerein-induced TNF-α and IL-1β inhibitory effect caused Nfkb1 downregulation and, hence, prevented apoptosis in osteoblasts. The increased ALP activity and IL-10 in PDG indicate that diacerein mitigates periodontitis impact on alveolar bone in rat molars.

This study aimed to analyse the impact of sea buckthorn (SB) berry extract on the function of cultured rat primary osteoblasts, including the production of bone metabolism-related biomarkers and bone matrix formation. Primary osteoblasts best reflect invivo conditions. Osteoblast apoptosis, viability, alkaline phosphatase (ALPL) activity, production of ALPL, osteocalcin (BGLAP), collagen type I alpha 1 (COL1A1), integrin-binding sialoprotein (IBSP), tumor necrosis factor ligand superfamily member 11 (TNFSF11), and calcium/collagen deposition were assessed. The composition of the extract showed that the main phenolic metabolites found were flavonol glycosides (67.1 %). SB berry extract significantly increased the levels of BGLAP (at 0.5 and 1 μg/mL), COL1A1 (at 1-100 μg/mL), IBSP (at 0.1-1 μg/mL), collagen deposition (at 1-10 μg/mL), and decreased TNFSF11 levels (at 0.1 and 0.5 μg/mL). Although higher doses of the extract (50 and 100 μg/mL) reduced osteoblast apoptosis, they also lowered cell viability, IBSP levels, and mineralization. It can be concluded that SB berry extract at concentrations up to 10 μg/mL favorably affected multiple bone metabolism-related biomarkers, indicating that it has encouraging potential for use as a nutraceutical to support bone health due to the unique composition of bioactive metabolites and the known synergistic interactions betweenthem.

Background/Objectives: Diabetic osteoporosis (DOP) is a metabolic bone disorder marked by reduced bone mass, impaired microarchitecture and elevated fracture risk arising from type 1 and type 2 diabetes. Understanding its pathophysiology is essential for developing effective interventions. Method: A broad literature search of Scopus and PubMed (2015-2025) using diabetic osteoporosis-related keywords identified relevant English in vivo studies, which were screened, extracted, and narratively summarised for this review. Results: In vivo models, including high-fat-diet (HFD), streptozotocin (STZ) and combined HFD + STZ protocols, are widely used to investigate DOP mechanisms. HFD models mimic obesity-induced insulin resistance, chronic hyperglycaemia and low-grade inflammation, leading to suppressed osteoblast activity, enhanced osteoclastogenesis and accumulation of advanced glycation end products (AGEs). Ultimately, they compromise bone microarchitecture and mechanical strength. STZ models replicate type 1 diabetes by inducing β-cell destruction, insulin deficiency, oxidative stress, osteoblast apoptosis and inflammatory pathways promoting bone resorption. The combined HFD + STZ model integrates insulin resistance and partial β-cell dysfunction, closely reflecting type 2 diabetes pathology, including trabecular bone loss, collagen glycation and disrupted osteoblast-osteoclast signalling. Mechanistically, DOP involves impaired insulin/IGF-I signalling, AGE-RAGE interactions, oxidative stress and inflammation, resulting in diminished bone formation and quality. These models provide robust platforms for exploring molecular mechanisms and evaluating potential therapies, including Wnt pathway modulators, antioxidants and ferroptosis inhibitors. Conclusions: Collectively, preclinical in vivo models are indispensable for understanding DOP pathophysiology and developing strategies to mitigate diabetic bone fragility.

Catalpol attenuates postmenopausal osteoporosis by activating SIRT1-mediated P53 deacetylation and inhibiting CASPASE-3-driven osteoblast apoptosis.

Exploring the role of metformin in high fluoride ingestion-induced bone lesions.

This article explores the pathophysiology of osteoporosis associated with androgen deficiency, a metabolic disorder characterized by inadequate levels of androgens or disruptions in androgen signaling. A focus is placed on the collaborative regulation of bone health by the immune and nervous systems. Notably, androgens are identified as critical modulators of immune responses, significantly influencing the development and progression of osteoporosis. The review highlights that androgens enhance erythropoietin (EPO) signaling, which exhibits dose-dependent effects on bone metabolism-physiological EPO levels promote osteoblast differentiation, while excessive EPO can induce osteoclastogenesis through the Janus kinase 2/Signal transducer and activator of transcription 5 (JAK2/STAT5) pathway. Importantly, the expression of EPO receptors (EPOR) is not confined to osteoblasts and osteoclasts but is also found on numerous immune cells, which suggests the potential for androgens to affect the EPO/EPOR signaling system and its implications for bone homeostasis. Additionally, androgens contribute to the management of osteoporosis by inhibiting osteoclastogenesis mediated by immune cells, promoting M2 macrophage polarization, decreasing Th17 cell differentiation, and lowering the Th1/Th2 ratio, ultimately leading to reduced Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) expression. Furthermore, the central nervous system plays a pivotal role by mitigating the overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, thereby lessening glucocorticoid-induced osteoblast apoptosis. In peripheral contexts, neuropeptides such as calcitonin gene-related peptide (CGRP) and Semaphorin 3A (Sema3A) promote osteogenesis. Moreover, androgens are shown to enhance neuromuscular junction functionality, providing additional mechanical stress that contributes to the maintenance of bone mass. This review aims to elucidate the intricate mechanisms governing bone homeostasis and proposes a novel therapeutic framework for the management of osteoporosis induced by androgen deficiency. By emphasizing the regulatory roles of androgens within the context of immune-neural interactions, this work provides valuable insights that may inform future treatment strategies. The target audience includes endocrinologists, rheumatologists, osteoporosis researchers, and clinicians involved in metabolic bone disease management.

BackgroundMicroRNAs play a crucial regulatory function in preserving bone remodeling balance and bone metabolic homeostasis.AimsThis study aimed to detect miR-202-5p expression in OP patients and investigate its role and potential regulatory mechanism in OP development.MethodsqRT-PCR was used to determine miR-202-5p and PTEN expression in serum. The receiver operating characteristic curve was utilized to evaluate miR-202-5p’s diagnostic value for OP. CCK-8 and flow cytometry were applied to determine the effects of miR-202-5p on the proliferation and apoptosis of human fetal osteoblasts. Luciferase reporter assay was conducted to verify the targeted binding between miR-202-5p and PTEN.ResultsmiR-202-5p in OP patients was markedly downregulated, and miR-202-5p exhibited high diagnostic value for OP. In vitro experiments showed that miR-202-5p promoted hFOB proliferation, inhibited apoptosis, and enhanced osteogenic differentiation. PTEN expression was significantly higher in OP patients. Prediction via the miRDB database indicated that PTEN might be a target gene of miR-202-5p, which was further confirmed by luciferase assay, verifying their interaction. Additionally, downregulation of PTEN significantly promoted osteogenic differentiation.ConclusionsmiR-202-5p holds promise as a novel potential diagnostic biomarker for OP. miR-202-5p may regulate osteoblast proliferation, apoptosis, and osteogenic differentiation by targeting PTEN, thereby exerting a role in OP.

ObjectiveOsteoporotic fractures (OPF) and delayed fracture healing (DFH) pose major health challenges for the elderly. The lncRNA SSTR5-AS1 shows abnormal expression in people with low BMD. Understanding how SSTR5-AS1 regulates fracture healing could help address DFH.MethodsThis study detected the expression levels of SSTR5-AS1, miR-193b-3p, osteogenic markers (RUNX2, ALP, BSP, OCN, OPN) mRNA, and apoptosis-related genes (Bcl-2, Bax, Bad) in osteoblasts and serum samples from all participants using RT-qPCR. Logistic regression was used to identify the independent factors influencing fracture healing. Cell proliferation and apoptosis were assessed using CCK-8 assays and flow cytometry, respectively. The binding relationship between SSTR5-AS1 and miR-193b-3p was validated through dual-luciferase reporter assays.ResultsSSTR5-AS1 is significantly downregulated in patients with OPF and DFH and negatively regulates the expression level of miR-193b-3p. SSTR5-AS1 is a protective factor for fracture healing. Elevating SSTR5-AS1 levels significantly reduces miR-193b-3p expression, thereby decreasing osteoblast apoptosis, increasing Bcl-2 expression, and decreasing Bax and Bad levels. Furthermore, enhancing SSTR5-AS1 promotes osteoblast proliferation, upregulates RUNX2, ALP, BSP, OCN, and OPN expression, and facilitates osteoblast differentiation.ConclusionSSTR5-AS1 demonstrates significant diagnostic value for OPF and DFH, making it a promising biomarker for these conditions. When overexpressed, SSTR5-AS1 reduces miR-193b-3p levels, promoting osteoblast proliferation and differentiation. This may accelerate fracture healing.

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and occurs in both high- and low-turnover bone disorders. While phosphate (P) control is known to reduce adverse effects, most supporting studies have focused on high-turnover models. This study evaluates the effects of two P binders-calcium carbonate (CaCO₃) and sevelamer carbonate-on laboratorial markers and bone histomorphometry in a low-turnover bone disease model. Wistar rats underwent 5/6 nephrectomy and total parathyroidectomy (Nx + PTx) to induce low-turnover bone disease. Animals were assigned to 4 groups: Sham, untreated Nx + PTx, Nx + PTx + CaCO₃, and Nx + PTx + sevelamer. After 8 weeks, we performed biochemical analysis, bone histomorphometry, gene expression (SOST, β-catenin, DKK-1), immunohistochemistry (sclerostin, β-catenin, FGF23, DKK-1), and apoptosis assays. Bone histology confirmed low-turnover disease in Nx + PTx rats, which also developed CKD and hyperphosphatemia. Both P binders effectively reduced serum P levels, but only CaCO₃ corrected hypocalcemia. Notably, CaCO₃ treatment led to increased osteoid parameters, elevated osteoblast surface and absence of tetracycline labeling - hallmarks of osteomalacia. Moreover, CaCO₃ increased osteoblast apoptosis. In a rat model of low-turnover bone disease with normal dietary P, high-dose CaCO₃ impaired bone mineralization and induced osteomalacia. These findings highlight potential risks of calcium-based phosphate binders in patients with low bone turnover and hyperphosphatemia, supporting the need for careful clinical consideration and monitoring.

ABSTRACTObjectiveGlucocorticoid‐induced osteonecrosis of the femoral head (GC‐ONFH) represents a devastating complication of steroid therapy, primarily driven by osteoblast apoptosis and impaired osteogenesis. Although selenium (Se) is renowned for its potent bone‐protective properties, its therapeutic potential, and specific mechanisms in GC‐ONFH remain largely unexplored and thus require further investigation.MethodsTo assess the therapeutic effectiveness of oral selenium supplementation in GC‐ONFH, a rat model of GC‐ONFH was utilized. The rats were randomly allocated into three groups (n = 6 per group): (1) Control group, (2) Methylprednisolone sodium succinate (MPS) group, and (3) Se group. The intervention was carried out for 4 weeks. In vitro experiments utilized primary rat osteoblasts and MC3T3‐E1 cells to elucidate the mechanisms through which selenium mitigates dexamethasone (DEX)‐induced alterations in cell proliferation, apoptosis, and osteogenic differentiation. The assessments were conducted using micro‐CT and histomorphometry, CCK‐8 assays and flow cytometry, as well as RT–qPCR, Western blotting, and immunofluorescence.ResultsSelenium supplementation effectively prevented trabecular collapse and significantly reduced the number of empty lacunae in rats with GC‐ONFH. Specifically, an optimal dose of 10 μmol Se successfully reversed the damage induced by DEX, including the restoration of cell proliferation, suppression of apoptosis, and rescue of osteogenic activity. Mechanistically, Se counteracts the DEX‐induced suppression of phosphorylated phosphatidylinositol 3‐kinase (p‐PI3K), phosphorylated protein kinase B (p‐AKT), and phosphorylated glycogen synthase kinase 3β (GSK3β) (p‐GSK3β), thereby activating the PI3K/AKT/GSK3β signaling pathway, which promotes cell proliferation, inhibits apoptosis, and enhances osteogenesis in osteoblasts.ConclusionSelenium can activate the PI3K/AKT/GSK3β pathway, reverse DEX‐induced hypoproliferation and apoptosis, restore osteogenic capacity, prevent trabecular collapse, and attenuate GC‐ONFH in rat models. Our findings demonstrate that selenium supplementation can be regarded as a clinically applicable strategy for impeding the progression of GC‐ONFH in at‐risk patients.

Osteoporosis (OP) is characterized by reduced bone mass and deteriorated bone structure, leading to an increased risk of fractures. Xiao Chai Hu Tang (XCHT), a traditional Chinese medicine, has shown promise in alleviating OP, but its underlying mechanisms remain unclear. This study aimed to identify the active compounds in XCHT, screen core targets related to postmenopausal osteoporosis (PMOP), and explore its therapeutic mechanisms. Active compounds in XCHT were identified using LC-Q-MS/MS, and PMOP-related targets were screened via protein-protein interaction (PPI) network analysis. Gene Ontology (GO) and KEGG pathway analyses were conducted to explore core signaling pathways, while invivo validation was performed using ovariectomized rats. Network pharmacology revealed 278 XCHT targets, with 145 related to PMOP. PPI analysis identified 20 core targets. GO and KEGG analyses suggested that XCHT may regulate gene expression, apoptosis, and inflammation via the MAPK signaling pathway. LC-MS identified 49 active compounds. Animal studies confirmed that XCHT mediates MAPK signaling to treat OP. Overall, the findings suggest that XCHT improves PMOP by regulating apoptosis and inflammation through the MAPK pathway, promoting osteoblast formation and reducing osteoblast apoptosis, providing valuable insights into its potential therapeutic role in PMOP.

BBOX1-AS1 ameliorate bone fracture by regulating cell viability and apoptosis of osteoblasts.