Constructing a cross-tissue human knee single-cell atlas identified osteoarthritis reduces regenerative tissue stem cells while increasing inflammatory pain macrophages

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 5, 2025

Osteoarthritis (OA) affects the entire knee joint; however, cross-tissue molecular mechanisms are poorly understood due to a lack of comprehensive, integrated analysis. We constructed first comprehensive single-cell RNA sequencing OA atlas from articular cartilage, meniscus, synovium, and subchondral bone which showed active communication between them. Healthy synovium meniscus contain largest populations tissue stem cells (TSCs) immune that altered in OA. The regenerative TSCs expressing SDF1, SOX9, CD146, PDGFRB, CD105 decrease during OA, whereas osteogenic differentiation-related factor NT5E (CD73) increased. In balance shifts state with an increased number TSCs. also report level quadruple-positive inflammatory (IL1B-IL6-NOS2-TNF) pain marker (P2RX7) specific macrophages Fibroblasts enriched OA-synovium may contribute fibrosis. Importantly, cartilage contains unique MMP13-producing detrimental chondrocytes along RUNX2-producing worsen pathophysiology. This provides novel avenue for potential therapeutic applications human other musculoskeletal diseases injuries, targeting intervene OA-specific cellular alterations.

Язык: Английский

New developments in osteoporosis, osteoarthritis and soft tissue repair

Journal of Orthopaedic Translation, Год журнала: 2024, Номер 49, С. A1 - A2

Опубликована: Ноя. 1, 2024

Язык: Английский