An experimental model of osteoarthritis resulting from laxity of the joint was induced in eighteen mature dogs (at least two years old) by sectioning the anterior cruciate ligament of the right knee (stifle) with a stab incision, the left knee providing a control. A sham operation was also performed in three other dogs, in which a stab incision was made but the ligament left intact. The dogs were killed at various intervals from one to forty-eight weeks later. Morphological changes in bone, cartilage, synovial membrane and joint capsule were examined in all the joints and biochemical changes in the cartilage of three dogs killed after two, eight, and sixteen weeks. All the changes resulting from the operation progressed with time and became indistinguishable from those found in three dogs with natural osteoarthritis of the knee. There were no changes in the joints which had sham operations. As the time of onset is known, this experimental model in a larger species enables a study to be made of the biochemical as well as the morphological changes in the early stages of osteoarthritis.
Biochemical changes in the articular cartilage of the knees of mature dogs, one with natural and four with surgically induced osteoarthritis, have been investigated. The four dogs were killed three, six, nine and forty-eight weeks after division of the right anterior cruciate ligament, the left knees serving as controls. The cartilage of the joints operated on was thicker and more hydrated than the control cartilage; the proteoglycans were more easily extracted and had higher galactosamine/glucosamine molar ratios. The proportion of proteoglycans firmly associated with collagen, and hence not extractable, diminished before fibrillation was demonstrable by indian ink staining of the surface. These biochemical changes were present throughout the entire cartilage of the joints operated on of the dogs killed more than three weeks later, and of the dog with natural osteoarthritis. The results suggest that in response to altered mechanical stresses the chondrocytes synthesise proteoglycans that contain more chondroitin sulphate relative to keratin sulphate than normally, as in immature articular cartilage.
1. Serial slices of articular cartilage obtained at necropsy from apparently normal femoral condyles of individuals between the ages of twenty-six and sixty were examined chemically, by electron microscopy and for permeability. 2. The most superficial layer was shown by chemical analysis and electron microscopy to have the highest collagen content, which fell sharply with distance from the articular surface. On the other hand the glycosaminoglycan content was very low in the superficial layers but increased with depth. This variation was found in all specimens tested but the absolute levels of collagen and of glycosaminoglycans were widely different. There was no correlation of chemical composition with age. 3. Collagen fibrils in the superficial layer were of much smaller diameter than in the deeper zones. 4. Hydraulic permeability was shown to depend more on glycosaminoglycan than on collagen content, although it varied inversely with both these factors. 5. The results obtained demonstrate clearly the close relation between the physical properties of cartilage and its chemical composition.
1. Mucopolysaccharides were analysed in the urine of thirteen patients with Morquio's syndrome aged between three and fifty-nine years and of fourteen controls of comparable ages. 2. There were no significant qualitative or quantitative differences between patients and controls. 3. The clinical and radiological findings suggested that these patients did not have the "Morquio-Ullrich" form of the disease, which appears on retrospective assessment of case reports to be more uniform and less diffuse than the Morquio-Brailsford form which may include a number of possibly unrelated diseases. 4. Keratosulphate has so far been demonstrated in the urine only of patients with the "Morquio-Ullrich" form of the disease, although the mucopolysaccharide excretion has been investigated in only a few patients with the Morquio-Brailsford form. The normal mucopolysaccharide excretion of the present series of patients suggests that a normal mucopolysaccharide excretion distinguishes the Morquio-Brailsford from the Morquio-Ullrich form, the latter having a number of features overlapping with Hurler's disease, where large amounts of mucopolysaccharide other than keratosulphate are excreted. 5. Both qualitative and quantitative analysis of urinary mucopolysaccharide are thus necessary to distinguish between Hurler's disease, the Morquio-Ullrich form and the Morquio-Brailsford's form of Morquio's syndrome.
