Femoral and tibial cartilage specimens from nonoperated, sham operated, and partially meniscectomized knees of New Zealand white rabbits were stujdied, using fluorescein-conjugated mouse IgG or 3 monoclonal antibodies (2G2, 2E9, and 6C9) that portrayed differing fine antigenic specificity for rabbit cartilage proteoglycan monomer. In nonoperated and sham operated animals, monoclonal antibodies 2G2 and 2E!3 stained cellular/pericellular (C/PC) and matrix areas; antibody 6C9 stained only C/PC areas. Augmented Ch'C and matrix staining of osteoarthritic femoral cartilage occurred with 2G2 and 6C9; tibial cartilage staiining was reduced. Increased 2E9 staining of C/PC regions was seen in tibial cartilage. The differential staiining patterns indicate that proteoglycan macromoleciular changes occur in experimental osteoarthritis and that these monoclonal antibodies can be utilized as probes for the connective tissue changes observed.Osteoarthritis (OA), a progressively destructive disease of the articular surfaces of joints, is characterized by localized erosion, fibrillation of the cartilage surface, osteophyte formation, and bony remodeling (1-3). Numerous etiopathogenic variables may be involved in the generation of these pathologic changes. These include mechanical stress, aging, genetic, enzymatic, and biochemical factors, as well as an immune response to sequestered cartilage cell surface antigens and matrix components (1,4-7).The extracellular matrix of articular cartilage consists mainly of large proteoglycan (PG) molecules interspersed in a meshwork of collagen fibers. Cartilage PGs exist in the form of nonaggregated subunit monomers, and of aggregates which contain monomer, hyaluronic acid, and link glycoproteins (8,9). PG monomeric subunit molecules are approximately 1 X lo6 daltons in molecular weight, and are composed of polypeptide chain(s) with numerous extended glycosaminoglycan side chains (10). The PG molecules are characterized by their wide polydispersity and large hydrodynamic volume in solution.Numerous researchers (1 1-14) have reported a reduction in the size and proportion of aggregates, and varying capacity of cartilage proteoglycans to form aggregated macromolecules in patients with OA. In this study, we generated monoclonal antibodies specific for rabbit PG monomer subunits, for the purpose of analyzing the structural differences in proteoglycans from normal and osteoarthritic rabbit cartilage. The data suggested that PG monomers in normal and osteoarthritic femoral and tibial cartilage differ, and that monoclonal antibodies are useful probes for studying the osteoarthritic changes.
MATERIALS AND METHODSPartial medial meniscectomy. Osteoarthritis was induced in rabbit knees by partial medial rneniscectorny ,