Extracellular matrix changes in knee joint cartilage following bone-active drug treatment
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Certain drugs or treatments that are known to affect bone quality or integrity might have side effects on the extracellular matrix of articular cartilage. We investigated the effects of vitamin D and calcium deficiency, estrogen deficiency, and hypercortisolism alone or in combination with bisphosphonates or sodium fluoride in an animal model, viz., the Göttingen miniature pig (n=29). The articular cartilage from knee joints was analyzed for its content of glycosaminoglycans (GAGs, as macromolecules responsible for the elasticity of articular cartilage) by a spectrometric method with dimethylene blue chloride. In cryo- or paraffin sections, alkaline phosphatase (AP, as an enzyme indicating mineralization or reorganization of articular cartilage matrix) was localized by enzyme histochemistry, and positive cells were counted, whereas differently sulfated GAGs were stained histochemically. A significant decrease in GAG content was measured in ovariectomized and long-term glucocorticoid-treated animals compared with untreated animals. In the glucocorticoid/sodium fluoride group, GAGs were significantly diminished, and significantly fewer AP-positive chondrocytes were counted compared with the control. GAG content was slightly higher, and significantly more AP-positive chondrocytes were counted in short-term glucocorticoid-treated animals then in the control group. GAGs, as part of proteoglycans, are responsible for the water-storage capacity that gives articular cartilage its unique property of elasticity. Thus, ovariectomy and long-term glucocorticoid therapy, especially when combined with sodium fluoride, have detrimental effects on this tissue.
KeywordsArticular cartilage Glycosaminoglycans Water content Bone-active drug treatment Göttingen miniature pigs
We thank Ms. R. Kirsch, Ms. C. Kremling, and Mr. F. Lichte for excellent assistance during the performance of the experiments, Dr. A. Caliebe (Department of Stochastics at the Mathematical-Natural Sciences Faculty, Kiel University) for help with the statistical evaluation of the data, and Horst Fischer and Jochen Kunze for conscientious animals care.
- Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM (1996) Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 125:961–968PubMedGoogle Scholar
- Burstone MS (1962) Enzyme histochemistry and its application in the study of neoplasms. Academic Press, New YorkGoogle Scholar
- Fernandez Lemos SM, Caldarini MI, Kofoed JA, Suarez CG, Davison MR, Palmieri JE (1988) Alteraciones en la matrix organica del hueso y cartilago de rata por el uso prolongado de fluoruro de sodio. Medicina (B Aires) 48:45–48Google Scholar
- Gallagher JA, Beresford JN, McGuire MKB, Ebsworth NM, Meats JE, Gowen M, Elford P, Wright D, Poser J, Coulton LA, Sharrard M, Imbimbo B, Kanis JA, Russell RGG (1984) Effects of glucocorticoids and anabolic steroids on cells derived from human skeletal and articular tissues in vitro. Adv Exp Med Biol 171:279–291PubMedGoogle Scholar
- Hardman JG, Limbird LE (2001) Goodman and Gilman's. The pharmacological basis of therapeutics. McGraw-Hill, New YorkGoogle Scholar
- Kaiser H, Kley HK (1997) Cortisontherapie. Corticoide in Klinik und Praxis. Thieme, StuttgartGoogle Scholar
- Meunier PJ (1996) Bone forming agents. In: Papapoulos SE (ed) Osteoporosis 1996, Proceedings of the World Congress on Osteoporosis, Amsterdam, pp 305–313Google Scholar
- Monier-Faugere MC, Geng Z, Paschalis EP, Qi Q, Arnala I, Bauss F, Boskey AL, Malluche HH (1999) Intermittent and continuous administration of the bisphosphonate ibandronate in ovariohysterectomized beagle dogs: effects on bone morphometry and mineral properties. J Bone Miner Res 14:1768–1778PubMedCrossRefGoogle Scholar
- Naka MH, Morita Y, Ikeuchi K (2005) Influence of proteoglycan contents and of tissue hydration on the frictional characteristics of articular cartilage. Proc Inst Mech Eng [H] 219:175–182Google Scholar
- Sachs L (1992) Angewandte Statistik - Anwendung statistischer Methoden. Springer, Berlin Heidelberg New YorkGoogle Scholar
- Scholz-Ahrens KE, Delling G, Stampa B, Barkmann R, Timm W, Schrezenmeir J, Glüer CC (2000) Bone mineral density and trabecular structure in steroid-induced osteoporosis in minipigs. J Bone Min Res 15:542Google Scholar