Analysis of osteoarthritic cartilage using monoclonal antibodies reactive with rabbit proteoglycan

Abstract

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 ,

Effect of Intradiscal Monopolar Pulsed Radiofrequency on Chronic Discogenic Back Pain Diagnosed by Pressure-Controlled Provocative Discography: A One Year Prospective Study

“…Modic changes, which involved disc and end-plate degeneration, are in some cases the result of mechanical and nutritional causes 35. Histologic specimen showed fibrovascular replacement in Modic type I degenerative disc 6.…”

Application of a semiautomatic classifier for modic and disk hernia changes in magnetic resonance

“…11 Genetic factors are consistently described in animal models, with degenerative disc disease at an early age in cases of familial osteoarthritis and stenosis of the lumbar canal. 12 Magnetic resonance imaging is the most important diagnostic method for clinical diagnosis of intervertebral disc disease. The characteristic signal is usually in disc T2, which best reflects changes in age and/or degeneration, 13 primarily in sagittal section.…”

A Case–control Study of Major Genetic Predisposition Risk Alleles in Developing DDD in the Northeast US Population: Effects of Gene–gene Interactions

“…4 LBP sits very high in the list of factors causing physical disability and has been ranked the sixth most burdensome condition in a recent Global Burden of Disease 2010 Study. 5 Ever since in 1986 it was first conjectured that an individual might be highly genetically predisposed to DDD, 6 a steady stream of studies has expanded the number of genetic variants associated with increased risk of developing the condition. [7][8][9][10][11] A large number of variants in a number of ''predisposition genes'' have now been reliably implicated in elevation of the risk of developing DDD.…”