Proteoglycan alterations during developing experimental osteoarthritis in a novel hip joint model

Abstract

Degenerative hip joint disease was induced in dogs by extra-articular surgery that created a condition that mimics hip dysplasia. Decreased acetabular coverage of the femoral head gave altered mechanical load, with ensuing cartilage degeneration. For comparison, degenerative knee joint disease was induced in other dogs by transection of the anterior cruciate ligament of the knee. The femoral head articular cartilage showed macroscopic signs of degeneration within a month. No macroscopical changes of synovitis were present. Chemical analysis of cartilage samples showed loss of proteoglycans. Guanidine hydrochloride extracts of the cartilage contained proteoglycan fragments that could be separated by equilibrium density gradient centrifugation in cesium chloride. The data indicate that proteoglycans are fragmented by proteolytic cleavage and lost from the cartilage. The proteoglycans remaining in the tissue are smaller and have lost the ability to aggregate with hyaluronic acid. Similarly, in experimental knee joint osteoarthritis, the proteoglycan content of the cartilage decreased. The structural changes of those proteoglycans remaining were of a different nature, with no changes in proteoglycan size or aggregation properties, possibly indicating that both degradation and repair took place in the knee articular cartilage and/or that fragments were rapidly lost from the tissue. This may follow from different surgical procedures, only the one used for the hip joint being extra-articular, or from the different anatomy and physiology of the hip joint and the knee joint.

The role of the cartilage matrix in osteoarthritis

“…39,40 At the time of fibrillation, cartilage swelling with increased thickness can be observed, 24,41 for example by using MRI. 42 These noticeable events in OA have underlying mechanisms, of course, but little is known of early molecular processes.…”

“…Malalignment of a joint can certainly participate in the development of OA; hip dys plasia is well known to predispose to hip OA. 24 Thus, several different mechanical problems have roles in OA, and cells might respond to the altered and potentially increased load in ways that lead to both initiation and propagation of disease. Further support for the importance of mechanical triggers comes from the lack of OA in joints that are immobilized, whether in animal models 25 or in patients who have a paresis affecting the joint.…”

Effects of mechanical vibration on DNA and proteoglycan syntheses in cultured articular chondrocytes

“…In fact, joints in animal models of osteoarthritis in which surgery is used to change joint motion abruptly initially show adaptation, but subsequently exhibit cartilage deterioration and malfunction. 1 Thus, mechanical loading is an important regulator of chondrocyte metabolism, and appears to be a prerequisite for maintaining normal cartilage matrix properties. Some in vitro studies have shown that a static mechanical load decreased proteoglycan and protein syntheses, 2-9 while a dynamic mechanical load (compression or stretch) stimulated the synthesis of these matrix constituents.…”

“…These studies have shown that loading enhances the tendon fibroblasts of embryonic chicks, promotes the healing of fractures in rabbits and rats, increases the concentration of insulin-like growth factor I (IGF-I) in the tendons and peripheral nerves of rats, and relieves neurogenic or musculoskeletal pain in humans. 1,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] While the mechanisms of action for these various effects remain unclear, they likely differ with different modes of vibration. 15,17,20 In this study, the effects of vibratory load on articular chondrocytes in vitro were assessed by changes in DNA and proteoglycan syntheses as measured by 3 4 (1 mCi/ml) and 3 H-thymidine (2 mCi/ ml) were obtained from NEN Life Science Products (Daiichi Pure Chemical Co., Tokyo, Japan).…”

Physical Diagnostics of Cartilage Degeneration

“…The PG content of OA cartilage is substantially lower than normal [115,143] and the degree of loss has been shown to correlate with the severity of the disease [143]. Histologic staining of OA tissue has demonstrated that the PG loss is nonuniform, with depth into the tissue, beginning at the articular surface and proceeding progressively inward [116,161].…”