Integrated Single-Cell and Spatial Transcriptomics Reveal Convergence on a Senescence-Associated B Cell-MIF Signaling Axis in Joint Aging and Osteoarthritis Progression.
4 affiliations
- 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China.
- 2Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 3Clinical and Translational Research Center for 3D Printing Technology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 4Department of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
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.
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BibTeX
@article{li2026integrated,
title = {{Integrated Single-Cell and Spatial Transcriptomics Reveal Convergence on a Senescence-Associated B Cell-MIF Signaling Axis in Joint Aging and Osteoarthritis Progression.}},
author = {Weida Li and Yi Wang and Yongqing You and Yue Cui and Jiayun Liu and Xingbiao Ma and QiuYu Zhu and Qiang Wu and Zanjing Zhai and Zuyan Lu and Kerong Dai and Ye Sun},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78543},
url = {https://europepmc.org/article/MED/42958787},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated Single-Cell and Spatial Transcriptomics Reveal Convergence on a Senescence-Associated B Cell-MIF Signaling Axis in Joint Aging and Osteoarthritis Progression.
AU - Weida Li
AU - Yi Wang
AU - Yongqing You
AU - Yue Cui
AU - Jiayun Liu
AU - Xingbiao Ma
AU - QiuYu Zhu
AU - Qiang Wu
AU - Zanjing Zhai
AU - Zuyan Lu
AU - Kerong Dai
AU - Ye Sun
PY - 2026
DA - 2026/10/29
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78543
UR - https://europepmc.org/article/MED/42958787
AB - 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.
SN - 2198-3844
ER -