Breakdown of proteoglycan and collagen induced in pig articular cartilage in organ culture.

Abstract

. (1975). Annals of the Rheumatic Diseases, 34, 303-311. Breakdown of proteoglycan and collagen induced in pig articular cartilage in organ culture. Explants of articular cartilage from young pigs were maintained in organ culture for 10-16 days, and degradation of matrix was induced by retinol or complement-sufficient antiserum. The percentage breakdown of proteoglycan and collagen (as hydroxyproline release) was measured. The response of the cartilage depended on whether or not the explants were cut so as to include some of the invading marrow ('invasion zone'). In media containing retinol, cartilage lost up to three-quarters of its proteoglycan whether the invasion zone was present or not, but very little of its collagen unless this region was included. In the presence of complement-sufficient antiserum, however, cartilage without the invasion zone was virtually unaffected, but both proteoglycan and hydroxyproline were released when invasion zone was included; here proteoglycan release began almost immediately, but there was a time-lag of 6-8 days before a substantial amount of hydroxyproline appeared in the medium. Histological examination of sample explants from the experiments supported the biochemical findings. The possible significance of the results in relation to rheumatoid arthritis is discussed.The mechanical, chemical, and biological properties of articular cartilage largely depend upon the molecular structure of the extracellular matrix, and loss of one or both of the two major polymers of matrix, i.e. proteoglycan or collagen, results in the drastic changes in properties observed in pathological conditions such as rheumatoid arthritis. To determine the enzymatic mechanisms of the disease process it is important to ascertain the sequence of events in cartilage erosion, and in particular the relative susceptibility of collagen and proteoglycan to degradation in the living tissue. In this investigation an attempt has been made to determine the relative rates ofcatabolism ofthese two molecules in resorbing articular cartilage.In previous work experiments were made to investigate the histological effects of excess of retinol (Barratt, 1973)

Establishment of glycosaminoglycan assays for mucopolysaccharidoses

“…Degradation of PGs occurs early in joint damage. The fragments of PGs are released into the synovial fluid and subsequently the blood [72,73]. This hypothesis is supported by the fact that KS levels in patients with MPS I, II, and VI are more elevated, compared with that in MPS III that results in less marked skeletal dysplasia.…”

The Effect of Synovial Tissue on the Breakdown of Articular Cartilage in Organ Culture

“…That the chondrocytes of isolated cartilage in culture, when stimulated by retinol in a concentration of 10 iu/ml medium, can digest the proteoglycan and to a lesser extent the collagen of the matrix has been demonstrated in previous work (9).…”

“…Van Gieson's stain colors the collagen of normal cartilage matrix a bright red, but when degradation of the collagen is in progress this coloration becomes increasingly faint and eventually is lost. Previous biochemical studies (9) have demonstrated a close qualitative correspondence between these staining reactions and the proteoglycan and collagen content of the cartilage.…”

Human Aggrecan Keratan Sulfate Undergoes Structural Changes during Adolescent Development

“…It is known that the degradation of proteoglycans occurs early in joint damage (43) and that fragments are released into the synovial fluid and subsequently the serum (44,45). The quantitation of keratan sulfates in both serum and synovial fluid has therefore been proposed as a measure of cartilage breakdown.…”