ADSC-enriched adipose extract alleviates cartilage fibrosis in temporomandibular joint osteoarthritis by inhibiting chondrocyte senescence.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease causing chronic pain and restricted mandibular movement. Its complex pathology and lack of effective therapies make it a clinical challenge. Recent studies have demonstrated that cartilage fibrosis correlates closely with TMJOA progression. Inflammatory microenvironments induce chondrocyte senescence, altering secretory phenotypes and driving fibrocartilage formation, characterized by hardened texture and poor mechanical properties, compromising joint biomechanics. Targeting cartilage fibrosis represents a key therapeutic strategy. Stem cell therapies show antifibrotic potential but face clinical limitations due to complex preparation and safety risks. METHODS: Synovial lavage fluid from TMJOA patients was collected and analyzed for fibrosis marker ACTA2 and inflammatory factor IL-1β expression to confirm intra-articular fibrosis and explore contributing factors. Adipose-derived mesenchymal stem cell (ADSC)-enriched adipose extract (ARDE) was prepared using mechanical emulsification with low-speed centrifugation. Its efficacy was assessed in a prospective clinical trial evaluating pain, mouth opening, and radiographic changes. ARDE's modulation of inflammation and repair of fibrocartilage were histologically assessed in a rabbit TMJOA model. In vitro TMJOA chondrocyte models induced by inflammatory factors (IL-1β, TNF-α) were co-cultured with ARDE's core component, ADSCs, to observe their impact on pathological chondrocytes. Transcriptome sequencing further explored their repair mechanisms. RESULTS: TMJOA patient synovial lavage fluid showed elevated fibrotic markers correlating significantly with disease stage and inflammation levels. Prospective clinical trial follow-up demonstrated that ARDE injection substantially improved pain, mouth opening limitation, and quality of life, with reduced joint effusion radiographically evident in some patients. In vivo, intra-articular ARDE promoted histological cartilage repair and extracellular matrix redeposition while downregulating inflammatory factors and fibrotic markers in articular cartilage. Mechanistically, inflammatory cytokine-stimulated chondrocyte models exhibited upregulated fibrotic and senescence-associated pathways; ADSC co-culture suppressed fibrotic marker expression and attenuated cellular senescence. CONCLUSION: ARDE effectively alleviates cartilage fibrosis by suppressing chondrocyte senescence, significantly restoring cartilage structure and alleviating disease symptoms. The preparation process meets clinical requirements, and its demonstrated safety and efficacy indicate promising clinical translation prospects. TRIAL REGISTRATION: Human studies were approved by the Medical Ethics Committee of The Third Affiliated Hospital of Air Force Medical University (Approval No: IRB-YJ-2022033) and were registered with the Chinese Clinical Trial Registry (Registration No: ChiCTR2300069677, registered 23 March 2023, https://www.chictr.org.cn/showproj.html?proj=184860 ).