BMSCs-Derived Exosomal XPO7 Attenuates Osteoarthritis Progression by Targeting KDM2B to Ameliorate Chondrocyte Senescence.

Authors

Xiaodong Mao, Guoliang Che, Mimi Zhang, Xiao Tan, Zhengzhi Liu

Published in

Journal of cellular biochemistry. Volume 127. Issue 10. Pages e70130.

Abstract

Chondrocyte senescence is a central driver of osteoarthritis (OA) pathogenesis. While bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) exhibit therapeutic potential, their key functional components remain unclear. We therefore investigated whether Exportin-7 (XPO7), a protein enriched in BMSCs-Exos, alleviates OA by ameliorating chondrocyte senescence-associated changes and explores the underlying mechanism. Using an IL-1β-induced in vitro OA model in rat chondrocytes, we treated cells with exosomes from BMSCs with modulated XPO7 overexpression or knockdown; KDM2B was overexpressed in chondrocytes. Senescence, apoptosis, viability, senescence-associated secretory phenotype (SASP) markers, and extracellular matrix (ECM) metabolism were evaluated. We found that BMSCs-Exos significantly mitigated IL-1β-induced chondrocyte senescence-like changes, apoptosis, SASP (p16, p21, p53, IL-1β, IL-6, TNF-α), and ECM degradation, as evidenced by the reversal of IL-1β-induced suppression of anabolic genes SOX9, COL2, ACAN and elevated catabolic gene MMP13. These protective effects were enhanced by XPO7 overexpression and diminished by its knockdown. Co-immunoprecipitation and immunofluorescence further showed that XPO7 physically interacted with and negatively regulated the histone demethylase KDM2B, and overexpressing KDM2B abolished the protective effects of XPO7-enriched exosomes. In an in vivo rat OA model induced by anterior cruciate ligament transection (ACLT), systemic administration of BMSCs-Exos overexpressing XPO7 attenuated cartilage destruction and improved mechanical allodynia (increased paw withdrawal threshold). These therapeutic benefits were significantly reversed by concurrent intra-articular injection with a KDM2B overexpressing plasmid. Collectively, BMSCs-Exos deliver XPO7, which negatively regulates KDM2B to attenuate chondrocyte senescence-associated phenotypes and OA progression. The XPO7-KDM2B axis may represent a promising therapeutic target for OA intervention.

PMID:
42829902
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

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