Healthy autologous synovium mitigates traumatic and inflammatory-based chondrocyte damage via increased IL-1Ra and TIMP-1 secretion

Introduction: Intrinsic responses of normal synovium to damaged cartilage are not well-understood. Objectives: To investigate if the addition of healthy synovium to damaged cartilage would improve cell viability and reduce the progression of osteoarthritic phenotypic features within the first 14 days after insult. Methods: Fresh human tali and femoral condyles from 7 human donors were collected and randomized to either IL-1β or impaction damage groups. In both experimental groups, control (no IL-1b or impaction damage) and treated cartilage explants were further randomized to synovium coculture (cartilage + synovium) or isolated cartilage culture. Samples from cartilage explants, synovium, and media were collected at 0, 2, and 14 days and assessed by Live-Dead assay, histology with hematoxylin and eosin and Safranin O, and ELISA for IL-1ra, TGF-β1, TIMP-1, PRG-4, TNFa, and FGF-2. Results: Both damage models demonstrated a greater percentage of live cells with the addition of synovium compared with cartilage alone (treated with IL-1b or impaction damage). In the IL-1β cartilage coculture, there was significantly greater IL-1Ra concentration compared with IL-1β cartilage culture, while the impacted cartilage coculture model first demonstrated a significantly greater concentration of TIMP-1 compared with the impacted cartilage culture at days 2 and 7, and subsequently greater IL-1Ra levels at days 7 and 14. Conclusions: Healthy synovium demonstrates a chondroprotective response with an associated rise in IL-1Ra (IL-1β and impaction models) and TIMP-1 (impaction model) after cartilage insult. These findings provide the basis for future investigation into the potential chondroprotective mechanisms of TIMP-1 and IL-1Ra.