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Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, and inflammation, leading to progressive joint dysfunction and pain. Current treatments offer limited disease-modifying effects, creating an urgent need for regenerative therapies. This study investigates the therapeutic efficacy of mesenchymal stem cell (MSC)-based interventions derived from bone marrow, adipose tissue, and synovial fluid in promoting cartilage repair and bone regeneration in OA. In vitro test determined that all MSC sources possessed very high cell viability and reported strong chondrogenic markers (SOX9, aggrecan, and collagen II) and anti-inflammatory cytokines (IL-10, TGF-β1 and PGE2) in response to inflammation excepted the bone marrow In order to assess intra-articular MSC injection efficacy, a live model of OA in rats caused by ACLT was used. Functional recovery improved substantially in the MSC-treated groups, with bone marrow derived MSCs showing the greatest improvement in gait score, weight-bearing and tolerance to pain. Results of the OARSI histological evaluation showed that cartilage in treated animals was significantly preserved, while bone marrow MSC-treated groups performance was the best. Further analysis using micro-CT showed enhanced regeneration of subchondral bone, where a higher bone volume fraction (BV/TV), thicker trabeculae (Tb.Th), lower trabecular spacing (Tb.Sp) were observed. Immunohistochemistry confirmed these findings: an up-regulation of cartilage-specific proteins as well as down-regulation of MMP-13 activity in MSC-treated joints. The combination of data shows that the bone marrow MSCs have remarkable regenerative and immunomodulating actions in OA, needing further translational and clinical studies..