Authors
Weida Li, Yi Wang, Yongqing You, Yue Cui, Jiayun Liu, Xingbiao Ma, QiuYu Zhu, Qiang Wu, Zanjing Zhai, Zuyan Lu, Kerong Dai, Ye Sun
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Oct 29, 2026. Epub Oct 29, 2026.
Abstract
Osteoarthritis (OA) involves age-associated structural and immune changes, yet whether senescence-associated B-cell states contribute to cartilage degeneration remains unclear. Integrated single-cell RNA sequencing and spatial transcriptomics of healthy, aged, and OA mouse joints identify reduced B-cell abundance but enrichment of a low-proliferative, inflammatory state with heightened macrophage migration inhibitory factor (MIF) signaling. Cell-cell communication and spatial ligand-receptor analyses identify enhanced predicted MIF-CD74/CD44 interactions in B-cell-associated regions adjacent to cartilage. Constitutive MIF deficiency attenuates senescence-associated B-cell changes, MMP13 induction, and cartilage damage in vivo. Joint-derived B cells from aged and OA mice induce chondrocyte senescence, reduce COL2A1 and HMGB1, and increase FN1 and MMP13 through MIF-dependent paracrine signaling. These effects are suppressed by MIF neutralization and restored by recombinant MIF in MIF-deficient co-cultures. A composite hydrogel carrying quercetin and MIF-siRNA-loaded PLGA microspheres for local co-delivery. The microspheres show gradual siRNA release over 96 h in vitro. In DMM-induced OA, the formulation reduces MIF, P16, and MMP13 signals, restores HMGB1, and preserves cartilage. These findings support a senescence-associated B cell-MIF signaling axis associated with joint aging and chondrocyte dysfunction and provide proof of concept for a local biomaterial-based strategy that attenuates OA-associated changes.
PMID:
42958787
Bibliographic data and abstract were imported from PubMed on 30 Oct 2026.
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