Correlation between articular cartilage collagenase activity and osteoarthritis

Abstract

Articular cartilage collagenase activity was determined for 28 sections obtained from twelve femoral heads. For each one square centimeter area, a section was graded by a histologic-histochemical grading system for the severity of the arthritis. Collagenase activity was found primarily in those areas of moderately severe disease, but not in mild or end stage arthritis.In examining joints with advanced or "end stage" osteoarthritis, one frequently encounters sites in which the articular cartilages have been totally lost with resultant exposure and eburnation of the underlying bony endplate. The mechanism by which this extensive degradation occurs is not completely understood, but there is ample evidence to indicate that at least a portion of the loss results from autolytic enzymatic digestion. Cathepsin D which acts optimally at a pH of 4.5 and neutral cartilage proteoglycanases which degrade the proteoglycan of the matrix have been described in several laboratories (1,2) and data have been presented Submitted for publication November 28, 1977; accepted in revised form June 7, 1978. which suggest that lysosomal activity varies directly with the severity of the osteoarthritis (3). The substrate of the catheptic lysosomal enzymes appears to be principally proteoglycan, but it would seem logical that a mechanism for destruction of the collagen also exists since total loss of substance does occur. Recently the presence of an articular cartilage collagenase which could not be detected in normal tissue was described in osteoarthritic cartilage (4).This observation is interesting in that it supports the possibility that end stage osteoarthritis may result from the action of cathepsin-neutral proteoglycanase (to destroy the proteoglycan) and collagenase activity to degrade the collagen. In order to confirm this hypothesis, it seems essential that a variation of collagenase concentration with severity of the diseases existed, particularly since prior studies from this laboratory had shown direct correlation of DNA, glycosaminoglycan ($6) and collagen synthesis (7) and concentration of hydrolytic enzymes (3) with advancing degrees of severity, particularly with mild and moderately severe osteoarthritis. To assess this, studies were performed on osteoarthritic femoral heads in which cartilage collagenase was compared with the severity of the disease process, as measured by a histologic-histochemical grading system (6) ( Table 1). MATERIALS AND METHODSTwelve human femoral heads, removed from patients at the time of replacement surgery, were obtained in the fresh state from the operating room. Eleven of the patients had the clinical diagnosis of osteoarthritis which was confirmed by

Bacterial lipopolysaccharides induce in vitro degradation of cartilage matrix through chondrocyte activation.

“…In contrast, the profile from explants incubated with 10 ,g LPS shows a decrease of high molecular weight species and a relative increase in lower molecular weight chondroitin the chondrocytes, to an increase in the rate of degradation of proteoglycan and collagen, or to a combination of both processes. It is generally believed that the degradative mechanisms play a major role in cartilage damage in noninflammatory arthritides (13,14). In chronic inflammatory arthritis, matrix degradation may be mediated by proteolytic enzymes in the synovial fluid, by the invasive pannus, or by the chondrocytes.…”

Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro

“…Also, proteases that are relevant for articular cartilage degradation might primarily diffuse in from the synovial fluid, originating in synovial cells (31,32) rather than articular chondrocytes. It is well known from biochemical studies that OA cartilage shows increased collagenolytic activity (9,33,34) and severe collagen denaturation and degradation (35).…”

Collagenolytic activity and collagen matrix breakdown of the articular cartilage in the pond‐nuki dog model of osteoarthritis

“…It may be that the enzyme was active in vivo and became latent upon homogenization and subsequent encounter with inhibitors. Alternatively, the (16)(17)(18).…”