Circular RNAs (circRNAs) serve as competing endogenous RNAs (ceRNAs) and indirectly regulate gene expression through shared microRNAs (miRNAs). However, the potential circRNAs functioning as ceRNAs in osteoporosis remain unclear. The bone marrow mesenchymal stem cells (BMSCs) were isolated from ovariectomy (OVX) mice and controls. We systematically analyzed RNA‐seq and miRNA‐microarray data, miRNA‐target interactions, and prominently coexpressed gene pairs to identify aberrantly expressed circRNAs, miRNAs, and messenger RNAs (mRNAs) between the OVX mice and controls. A total of 45 circRNAs, 22 miRNAs, and 548 mRNAs were significantly dysregulated (fold change > 1.5; p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted for differentially expressed mRNAs, and subsequently a circRNA‐associated ceRNA network involved in osteoporosis was constructed. We identified two ceRNA regulatory pathways in this osteoporosis mouse model—novel circRNA 0020/miR-206-3p/Nnmt and circRNA 3832/miR-3473e/Runx3, which were validated by real-time PCR. This is the first study to elucidate the circRNA-associated ceRNA network in OVX and control mice using deep RNA-seq and RNA-microarray analysis. The data further expanded the understanding of circRNA-associated ceRNA networks, and the regulatory functions of circRNAs, miRNAs and mRNAs in the pathogenesis and pathology of osteoporosis.

An imbalance between the adipogenesis and osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is considered the basic pathogenesis of osteoporosis. Although actin cytoskeleton remodelling plays a crucial role in the differentiation of BMSCs, the role of actin cytoskeleton remodelling in the adipogenesis of BMSCs and postmenopausal osteoporosis (PMOP) has remained elusive. Glia maturation factor-beta (GMFB) has a unique role in remodelling the polymerization/depolymerization cycles of actin. We observed that GMFB expression was increased in bone tissue from both ovariectomized (OVX) rats and PMOP patients. GMFB knockout inhibited the accumulation of bone marrow adipocytes and increased bone mass in the OVX rat model. The inhibition of adipocyte differentiation in GMFB knockout BMSCs was mediated via actin cytoskeleton remodelling and the Ca²⁺-calcineurin-NFATc2 axis. Furthermore, we found that GMFB shRNA treatment in vivo had favourable effects on osteoporosis induced by OVX. Together, these findings suggest a pathological association of the GMFB with PMOP and highlight the potential of the GMFB as a therapeutic target for osteoporosis patients.

Aims: This study aimed to investigate the relationship between physical activity (PA) and the risk of osteoarthritis (OA) and its subtypes.Methods: We included participants from the UK Biobank aged 37 to 73 years from February 2006 to June 2010. Baseline PA levels were categorized as high (≥ 3,000 metabolic equivalent of task (MET)-min/week), moderate (600 to < 3,000 MET-min/week), or low PA (< 600 MET-min/week) based on current public health guidelines. The associations between PA and OA and its main subtypes (hand, hip, and knee OA) were analyzed using Cox-proportional hazard models. The mediating role of BMI was tested under a causal counterfactual framework.Results: The median follow-up period was 12.50 years, with 25,036 incident total OA cases. Compared to low PA, we found no significant association between moderate PA and total OA risk. However, high PA significantly increased the risk of total OA by 19% (hazard ratio (HR) 1.19, 95% CI 1.15 to 1.23). This result is consistent with knee OA and hip OA, where HR was 1.25 (95% CI 1.19 to 1.31) for knee OA risk and 1.17 (95% CI 1.10 to 1.24) for hip OA risk, respectively. Moderate PA was associated with 14% (HR 0.86, 95% CI 0.76 to 0.97) reduction in the risk of hand OA. Moreover, we found that BMI mediated the association between PA and OA risk, with the mediating proportion for total OA, hand OA, knee OA, and hip OA, at 75.48%, 2.42%, 10.20%, and 51.39%, respectively.Conclusion: These findings suggest that high levels of PA increased the risk of total OA, as well as knee and hip OA, while moderate levels of PA significantly mitigate the risk of hand OA. BMI appears to mediate the relationship between PA and OA risk. Future research should elucidate the underlying mechanisms.Cite this article: Bone Joint Res 2025;14(7):656–665.