GPx3 marks adipocyte lineage commitment in bone marrow stromal cells

作者：Zhongxiang Wang, Yang‐Yang Hu, Li Mao, Xiaojun Chen, Chengyu Zhou, Zhiyang Xu, Kai Chen, Lichuang Wu · 发表于：Journal of Orthopaedic Surgery and Research · 年份：2025 · DOI：10.1186/s13018-025-05908-8 · 被引用次数：3 · 研究领域：Bone Metabolism and Diseases、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Mesenchymal stem cell research

BACKGROUND: Bone marrow adipose tissue (BMAT) plays an essential role in skeletal health and systemic metabolism, particularly under conditions of ageing and osteoporosis. Despite increasing recognition of BMAT as an active endocrine organ, the molecular mechanisms underlying its formation and expansion remain incompletely understood. METHODS: We conducted a transcriptomic re-analysis of publicly available datasets focused on the adipogenic differentiation of bone marrow stromal cells (BMSCs). Differential gene expression and pathway enrichment analyses were performed to identify key molecular changes. Validation was conducted at both the transcript and protein levels. Furthermore, re-analysis of single-cell RNA sequencing (scRNA-seq) data was employed to determine the cell type-specific expression of candidate genes within the bone marrow. Functional assays using RNA interference were carried out to investigate the role of glutathione peroxidase 3 (GPx3) in adipogenesis. RESULTS: Our analysis revealed a consistent activation of oxidative stress-related pathways during adipogenic differentiation. Among the upregulated antioxidant enzymes, GPx3 was selectively increased during adipogenic-but not osteogenic-differentiation. This pattern was validated at both mRNA and protein levels in vitro. scRNA-seq analysis showed that GPx3 expression is predominantly localized in BMSCs and adipocytes, with reduced expression observed in aged mice, corresponding to elevated levels of adipocy...