Expression of proteoglycan epitopes in articular cartilage repair tissue

Abstract

To determine if expression of specific proteoglycan epitopes distinguishes articular cartilage repair tissue from normal articular cartilage, we used seven monoclonal antibodies to examine normal articular cartilage and cartilage repair tissue from osteochondral defects 3.2 mm in diameter and 4.0 mm deep in the medial femoral condyles of 27 New Zealand white rabbits and seven cynomolgus monkeys. Following creation of the osteochondral defects, one limb of each animal was treated with cast immobilization while the other limb was treated with passive motion for two weeks. Rabbit knees were examined at eight (13 animals, 26 knees) and 36 weeks (14 animals, 28 knees) and monkey knees at eight weeks (seven animals, 14 knees) following surgery. Staining for six of the antibodies did not differ between repair cartilage and normal articular cartilage, but an antibody that recognizes atypical glycosaminoglycan structures in developing tissues (MAb 7D4) consistently distinguished repair cartilage from normal cartilage in rabbits and monkeys. Repair tissue consisting of hyaline toluidine blue-staining matrix containing chondrocytic cells uniformly showed strong 7D4 staining. In contrast, normal articular cartilage and fibrous repair tissue showed inconsistent weak 7D4 staining. At eight weeks following surgery, rabbit cartilage repair tissue stained more intensely for 7D4 than monkey cartilage repair tissue; in rabbits, cartilage repair tissue stained more intensely for 7D4 at eight weeks than at 36 weeks following surgery. Repair tissue staining for 7D4 did not differ between osteochondral defects treated with passive motion and those treated with immobilization in rabbits and monkeys. These results indicate that expression of a high level of proteoglycan epitope 7D4 distinguishes hyaline articular cartilage repair tissue from normal articular cartilage and fibrous cartilage repair tissue in the early stages of osteochondral healing, and that as hyaline articular cartilage repair tissue matures expression of 7D4 decreases. The ability to characterize repair cartilage proteoglycans with monoclonal antibodies may aid in the evaluation of the quality and maturity of cartilage repair tissue and thereby facilitate improvements in procedures for resurfacing joints.