Role of WNT Agonists, BMP and VEGF Antagonists in Rescuing Osteoarthritic Knee Cartilage in a Rat Model

Introduction The superficial zone of articular cartilage (AC) is vital for its function and biomechanics. The damaged AC gets vascularized and undergoes hypertrophy and ossification. Studies have highlighted these two as the major causative factors in osteoarthritis (OA). We aimed at preventing the OA progression in a rat knee instability model by inhibiting the vascular ingrowth and ossification using VEGF and BMP antagonist. A WNT agonist was also used to promote AC regeneration because of its protective effect on the superficial layer. Methods Rat knee OA was created by surgical excision of the medial meniscus and medial collateral ligament. Forty rats were divided into two groups of twenty each for surgical control and tests (surgery + intra-articular injection of drugs every two weeks). Ten animals from each group were sacrificed at four and eight weeks. Histology was mainly used to evaluate the outcome. Results A surgical OA model was successfully created with higher histological scores for operated knees, both in short- ( P = 0.0001) and long-term ( P = 0.001). Modified Mankin score was lesser in the test animals as compared to control ( P = 0.17) in the short-term, but the trend was reversed in the long-term ( P = 0.13). Subgroup analysis revealed that repeated injections in the anterolateral compartment contributed to higher scores in the lateral ( P = 0.03) and anterior ( P = 0.03) compartment of the knee in the long-term. Conclusion The combinatorial approach was effective in controlling the OA in short-term. Further studies are needed to test the sustained drug delivery system to improve the outcome.