Molecular approach to the understanding of osteoarthrosis

Abstract

The experimentally induced arthrosis discussed in this article reproduces the changes in the joint and the biochemical changes in the cartilage that are seen in naturally occurring canine osteoarthrosis. These changes are similar to those observed in human osteoarthrosis. The experimental model enables the early events to be studied so that a chronological sequence may be established. Changes occur first in the areas where lesions will later develop, they then spread to areas immediately surrounding lesions and finally the entire cartilage of the joint is involved even where lesions do not develop. In the present experimental model of osteoarthrosis there appear to be three phases. Phase 1 (1-3 weeks after surgery). Minimal histological changes take place and only area A of the tibial cartilage and a focal area of the femoral cartilage are affected. The changes include increased water content and extractability of proteoglycans and increased molar ratio of galactosamine : glucosamine of the tissue. Phase 2 (3-12 weeks after surgery). Erosion of the cartilage of area A develops and is accompanied by some loss of water and proteoglycans from this region. Elsewhere the changes that are localized in the first phase spread to all the remaining cartilage of the joint. Phase 3 (12-48 weeks after surgery). Severe erosion of focal sites now develops and in these sites water content decreases and there is a marked loss of proteoglycan. Throughout the remaining cartilage the changes seen in phase 2 become more marked, particularly the increase in extractability of proteoglycans. Only in the third phase would the disease be recognized by its pathology or radiology as osteoarthrosis. Osteoarthrosis is a particularly difficult disease to study experimentally, but as it occurs in many species, unlike rheumatoid arthritis, it is possible to study the genuine disease in animals. An opportunity thus exists to search for drugs that may delay its progress or even prevent the disease, although it is extremely unlikely that at advanced stages it is reversible to any significant extent. Because it is such a widespread disease, the benefit to the community would be enormous if its progress could be arrested or even delayed when clinical signs are first noted. The drugs that are at present prescribed for osteoarthrosis have been developed for the treatment of entirely different diseases. Whether they are of real benefit to patients is questionable and some may even be harmful particularly if given for long periods of time. In its initial stages osteoarthrosis appears to involve profound changes in the metabolism of cartilage cells set in train by increased hydration of the tissue; only at advanced stages does it become degenerative. At what stage the metabolic changes are reversible is a question of crucial importance in understanding the disease process and in attempting to develop effective therapeutic measures.