Cellular mechanisms involved in the breakdown of articular cartilage

Jubb, Ronald William (1980) Cellular mechanisms involved in the breakdown of articular cartilage. MD thesis, University of Glasgow.

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Abstract

In most of the major diseases in rheumatology the chronic disabling factor is the loss of joint function through destruction of articular cartilage. The exact pathogenesis of the cartilage loss in these diseases is unknown and a clearer understanding of the precise mechanisms involved is essential for the formulation of specific therapy. An organ culture system has been used to study the possible role of different articular cells and tissues in the destruction of cartilage matrix. This technique provides a closed, controlled environment in which to examine the potential capabilities of living tissues. Most of the work has been done on articular tissues from normal young pigs. It was impossible to dissect equivalent explants of synovium but finely divided synovial tissue explanted in measured volumes gave viable cultures. Minced synovial tissue causes a drastic breakdown of articular cartilage when the two tissues are cultured in contact and there is loss of proteoglycan and collagen by 14 days. This effect is also seen in dead cartilage. Dead cartilage, however, is unaffected by synovial tissue if the two explants are not in contact, whereas living cartilage becomes depleted of proteoglycan and collagen with fibroblastic transformation of some of the chondrocytes. Thus, synovial tissue has a direct, presumably enzymatic effect on cartilage matrix and also an indirect destructive effect mediated through the chondrocytes. This destructive effect is not confined to synovial tissue, and it has been shown that non-articular tissue such as blood vessel also produces both a direct and an indirect destructive effect on the cartilage matrix. That chondrocytes of isolated cartilage have the ability to destroy cartilage matrix has been confirmed by the action of retinol on isolated cartilage. After 16 days' exposure to 5 or 10 iu retinol/ml culture medium there is almost total loss of proteoglycan and extensive breakdown of collagen with fibroblastic transformation of the chondrocytes. There is a regional variation in the degree of destruction which is greatest in the deeper zone. The extent of cartilage matrix loss depends on the net effect of the various destructive processes. This is clearly demonstrated by the action of hyperoxia (55% O[2]) on cartilage and synovium. Hyperoxia increases the breakdown by synovial tissue of the collagen of cartilage matrix, stimulates the release of collagenase from the synovium but inhibits the indirect collagenolytic effect. An attempt has been made to study the role of the mononuclear leucocytes in the destruction of cartilage since these cells are found in large numbers in the synovium in chronic inflammatory arthritis. Cells obtained from the peripheral blood of young pigs greatly enhance the destructive effect of the synovium on the cartilage; the small number of monocytes present plays an essential part in the action of the leucocytes. Stimulation with phytohaem- agglutinin did not enhance the breakdown induced by the cells from peripheral blood but increased that caused by cells derived from lymph glands. The maintenance of cartilage matrix depends on the dynamic balance between synthesis and breakdown of the structural macromolecules. Some earlier results suggested that the synovium might impair the synthesis of proteoglycan by the chondrocytes as well as degrading the existing matrix. This has been examined in detail by studying the incorporation of [35]SO[4] into proteoglycan. The synovium was found to inhibit the synthesis of proteoglycan by chondrocytes in the original explant, but cells that have emigrated from the explant seem to be unaffected and often form new cartilage on the cut surface of the old. The inhibitory effect of the synovium is reversible. Some preliminary experiments have been made on human articular cartilage in culture. Pig synovial tissue, which has such a destructive effect on pig cartilage, causes little breakdown of matrix in human cartilage from the femoral head during 16 days' cultivation. On the other hand, it severely inhibits the synthesis of proteoglycan by the human chondrocytes. These results demonstrate the complexity of the processes involved in the breakdown of cartilage. They also show that the actions and interactions of the different tissues can be dissected apart by means of the organ culture technique to provide a better insist into the mechanisms involved. This should allow a more rational approach to the study of the pathogenesis of cartilage destruction in vivo.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Dame Honor
Keywords: Medicine
Date of Award: 1980
Depositing User: Enlighten Team
Unique ID: glathesis:1980-72109
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 12:58
Last Modified: 17 May 2019 12:58
URI: http://theses.gla.ac.uk/id/eprint/72109

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