Single-cell atlas reveals age-related cellular shifts underlying fibrosis in murine synovium
Bortolotti, O.; Marineche, L.; Abasi-Ali, B.; Severac, D.; Leccia, F.; Duperray, C.; Brugioti, L.; Colinge, J.; Bertrand-Gaday, C.; Sebti, S.; Apparailly, F.; Courties, G.
Show abstract
Aging is a major risk factor for joint disease, yet the impact of physiological aging on the synovium remains poorly defined. Here we generate a single-cell atlas of murine ankle synovium across age and identify the sublining stromal-myeloid niche as a major site of age-associated remodeling. Aging shifted fibroblast states toward oxidative stress and matrix-remodeling programs, accompanied by sublining collagen accumulation, reduced cellularity, and loss of THY1+ sublining fibroblasts. In parallel, resident synovial macrophages exhibited altered inflammatory and phagocytic responses together with a preferential decline in TIM4+VSIG4- sublining macrophages, without overt local myeloid expansion despite systemic inflammaging. Macrophage depletion experiments further supported a link between sublining macrophages and extracellular matrix homeostasis. Together, these findings provide a reference framework for synovial aging and uncover niche-specific stromal and macrophage alterations associated with aging.
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