SUMMARY Section of the anterior cruciate ligament has been performed in the knee of 11 mature dogs. The macroscopically normal cartilage from patella and femoral trochlea of animals killed from 2 to 32 weeks after operation was used for histological, histomorphometrical, and biochemical analysis. Previously undescribed degenerative lesions of the superficial matrix were observed, and there was evidence for secondary healing of these lesions. An early and progressive decrease in superficial cell density and a later progressive increase in cartilage thickness without any change in the cell density of the middle and deep cartilage layers was found. A slight increase in water content with no reduction in glycosaminoglycan content was observed. The results suggest that joint laxity results initially in superficial degenerative changes and later in hypertrophic regenerative changes due to cell proliferation and increased matrix synthesis. Hypertrophic remodelling of articular cartilage in response to abnormal mechanical stresses is postulated.Experimental osteoarthritis offers a unique opportunity for the study of the initial events leading to cartilage destruction, which is the main characteristic of the disease. Various models of osteoarthritis can be used,' but joint laxity induced by section of a cruciate ligament of the knee or meniscectomy is now considered the most valid method.2-6 Joint-laxityinduced osteoarthritis has been used for numerous biochemical and metabolic studies, and changes in water content and proteoglycan preceding the appearance of cartilage fibrillation have been demonstrated.4 5 In contrast the early histological changes are far less documented, and histomorphometric data are still lacking.Here we report the results of a study of the qualitative and quantitative histological changes preceding cartilage fibrillation induced by section of the anterior cruciate ligament of the dog's knee. We restricted the study to the cartilage of the patella and femoral condyle, which is only slowly affected by fibrillation. Histological data were correlated with glycosaminoglycan and water content. were used. They were of unselected breed and of both sexes, were 3 to 8 years old, and weighed 16 to 30 kg. Absence of prior osteoarthritis was established by clinical examination and during surgical procedures. The dogs were anaesthetised with intravenous sodium pentothal. The anterior cruciate ligament in the right knee of each dog was exposed through a median parapatellar incision and transected with a scalpel, care being taken to avoid damage to the articular surfaces. The left knee was used as control. No sham operations were performed, since no cartilage changes have been shown to be induced by this procedure.5 Postoperatively all animals were kept in pens large enough to allow walking and running. They were killed at regular intervals with an overdose of sodium pentothal, the duration of survival varying from 0 5 to 8 months after surgery.Preparation ofsections. Immediately after killing, both knees were op...

Liver samples from patients with three different types of liver diseases, alveolar echinococcosis (a dense and irreversible fibrosis), hepatocellular carcinoma and alcoholic cirrhosis, were analyzed for their content in hydroxypyridinium cross-links found in mature collagen. We demonstrated the presence of small amounts of pyridinoline in control livers (0.27 +/- 0.06 pmol/pmol of collagen). Pyridinoline content was increased in fibrotic livers, with the highest values found in patients with alveolar echinococcosis (up to 1.33 pmol/pmol of collagen). The deoxy analogue of pyridinoline was not detected in either normal or fibrotic livers. Pyridinoline levels, expressed as picomoles per picomole of collagen, were similar in all patients with carcinoma (0.7 +/- 0.05 pmol/pmol of collagen). They were heterogeneous in patients with alveolar echinococcosis and were particularly high in patients with alcoholic cirrhosis (1.04 +/- 0.11 pmol/pmol of collagen). These results demonstrate for the first time the presence of an hydroxypyridinium cross-link in liver fibrosis and suggest that pyridinoline measurement might be an important criterion in assessing the irreversibility of human liver fibrosis.

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