A13 INTRAARTICULAR LUBRICIN SUPPLEMENTATION IS CHONDROPROTECTIVE AND PREVENTS CARTILAGE DEGENERATION IN EXPERIMENTAL OSTEOARTHRITIS

Abstract

12 weeks post-BTM while Group C were sacrificed 12 [n = 6], 24 [n = 6] and 52 [n = 6] weeks post-BTM. At necropsy, both medial compartments of BTM joints were scored by 2 blinded observers for AC lesions and osteophytes (OP) using a 0−4 scale. Synovial tissue and a 5mm wide coronal osteochondral slice were removed from the mid-line of the femur and tibia and processed for histochemical and histomorphometric analyses using published methods. Intact patellae were used for topographical biomechanical AC indentation studies. Results: Gross morphological scores 12 wks post BTM showed a dosedependent effect of MPC on AC integrity and OP formation; 100 mil MPC emerging as the most effective chondroprotective dose relative to HA alone. Total AC score ratios (HA+MPC)/(HA) showed 100>150>25=10 while OP ratios were 100>25>10>150 mil MPC. Statistically significant (SS) lower scores were observed for total femoral & tibial AC (p = 0.019) and total AC and OP (p = 0.009) for Group C MPC joints compared HA alone. Histomorphometric analysis of Group C MPC+HA tibial plateaus revealed that AC were thicker than the corresponding HA-AC in the middle (p = 0.057) and outer regions (p = 0.028); for all regions (p = 0.01). The mean phase lag for the patellae AC of Group C MPC injected joints was significantly lower than the contralateral patella AC (p = 0.002). Mean modified Mankin scores for AC sections from Group C MPC+HA joints were less than corresponding HA sections but were not SS. There was no evidence of synovial histopathology modulation. The chondroprotective effects observed for the 100 mil MPC injected joints diminished with time; the positive effects noted at 12 and 24 weeks BTM being lost by 52 weeks. Conclusions: This is the first report, as far as we are aware, of a beneficial therapeutic effect of allogenic Stro-3+ MPC on cartilage integrity in a model of early OA. MPC/MSC are known to release growth factors and cytokines and also suppress the production of TNF-alpha by other cells, while up-regulating anti-inflammatory cytokines (eg. Il-4, Il-10). These paracrine activities of MPC could stimulate chondrocyte biosynthesis of new matrix but also attenuate local production and activity of catabolic mediators. The finding in this study that 100 million MPC were chondroprotective was consistent with such a mechanism of action.