Early degradation of type IX and type II collagen with the onset of experimental inflammatory arthritis.

Abstract

To determine whether following the onset of intraarticular inflammation, there is early damage to articular cartilage, specifically to types II and IX collagen, and the proteoglycan (PG) aggrecan, and whether measurement of the degradation products of these molecules in synovial fluid (SF) and serum may permit the detection of cartilage damage. A rabbit model of rheumatoid arthritis, antigen (ovalbumin)-induced arthritis, was studied. Articular cartilage samples were analyzed by immunoassays for total type II collagen content, its denaturation and cleavage by collagenases, and for type IX collagen content. PG content was determined by colorimetric assay. In serum and SF, total PG content and collagenase-generated peptides of type II collagen were measured. After 6 days, both the PG content and the NC4 domain of type IX collagen were reduced in femoral and tibial cartilage, concomitant with the onset of arthritis. In only the tibial cartilage did this reduction in PG persist up to day 20. However, denatured type II collagen was increased in all cartilage samples, but only on day 20. In SF, the PG content was significantly reduced on day 20, and products of type II collagen cleavage by collagenase were significantly increased on both day 6 and day 20. This study, which is the first of its kind examining changes in both types II and IX collagen and PG content, reveals early damage to both types of collagen as well as to PG in articular cartilage samples following induction of joint inflammation. SF analyses reveal this early damage and may be of value in the study and treatment of inflammatory arthritic diseases such as rheumatoid arthritis.