Curcumin controls the senescence of adipose-derived mesenchymal stem cells via the FoxO3/autophagy signaling pathway to enhance joint homeostasis for osteoarthritis therapy

作者：Rui Zhang, Lei Huang, Meng Jin, Haiyang Kou, Jie Ma, Jie Ma, Weijie Zhang, Jianbing Ma, Jianbing Ma · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04836-y · 被引用次数：8 · 研究领域：Osteoarthritis Treatment and Mechanisms、Mesenchymal stem cell research、Bone Metabolism and Diseases

BACKGROUND: Osteoarthritis (OA) is a common chronic and degenerative disease, the pathophysiological features of which involve the whole joint. In recent years, adipose tissue-derived mesenchymal stem cells (ADSCs) have attracted much attention in the field of regenerative medicine. Nonetheless, with aging in vivo or exogenous stress in vitro, mesenchymal stem cells undergo cellular senescence, resulting in limited therapeutic efficacy. Curcumin is a natural polyphenolic compound that has antioxidative, anti-inflammatory and antiapoptotic properties. We aimed to investigate the function and molecular mechanisms of the effects of curcumin on ADSC senescence and to explore the therapeutic efficacy of curcumin-pretreated ADSCs in OA management. METHODS: Mouse primary ADSCs were identified using immunofluorescence staining and multilineage differentiation. Cell counting kit-8 (CCK-8) assays, reactive oxygen species (ROS) level measurements, β-galactosidase staining, Western blotting, immunofluorescence staining, and transmission electron microscopy (TEM) were performed to explore the function of curcumin in ADSCs. Bioinformatics analysis, chromatin immunoprecipitation (ChIP), small interfering RNA (siRNA), and real-time quantitative PCR (RT‒qPCR) were performed to evaluate whether FoxO3 directly regulates Becn1. In vivo, adult C57BL/6 male mice were subjected to destabilization of the medial meniscus (DMM) to establish an OA model. Histological staining with HE and Safranin O and...