Inhibition of relaxin-induced pubic symphyseal “relaxation” in guinea pigs by glycosaminoglycan polysulfates and pentosan polysulfate
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There are similarities between the actions of estrogen and relaxin on the connective tissues of the pubic symphysis and those of neutral proteases on cartilage in osteoarthritis, including cartilage hydration, proteoglycan loss, and dissolution of collagen fibers.
We hypothesized that compounds known to inhibit cartilage breakdown in animal models of osteoarthritis, such as polysulfated GAGs, would also antagonize the actions of estrogen and relaxin that increase the laxity and mobility of the pubic symphyses of guinea pigs.
Estrogen-primed guinea pigs were injected with relaxin or with relaxin and the test compound. The pubic symphyses were manually palpated 6 h later and the degree of mobility scored. Glycosaminoglycan polysulfates and pentosan polysulfate inhibited relaxin-induced pubic symphyseal relaxation, whereas other types of agents were without effect.
The guinea pig pubic symphysis assay for relaxin may thus provide a novel rapid screening test for compounds with potential chondroprotective activity.
Key wordsChondroprotective drugs Proteoglycanase inhibitors Osteoarthritis model Cartilage breakdown Relaxin
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- L. C. Miller and C. A. Dinarello,Biologic activities of interleukin-1 relevant to rheumatic diseases. Pathol. Immunopathol. Res.6, 22–36 (1987).Google Scholar
- H. B. Fell and R. W. Jubb,The effect of synovial tissue on the breakdown of articular cartilage in organ cultures. Arth. Rheum.20, 1359–1371 (1977).Google Scholar
- T. Krakauer, J. J. Oppenheim and H. E. Jasin,Human interleukin-1 mediates cartilage matrix degradation. Cell Immunol.91, 92–99 (1985).Google Scholar
- J. Saklatvala, S. J. Sarsfield and L. M. C. Pilsworth,Characterization of proteins from human synovium and mononuclear leukocytes that induce resorption of cartilage proteoglycan in vitro. Biochem. J.209, 337–344 (1983).Google Scholar
- E. M. O'Byrne, H. C. Schroder, C. Stefano and R. L. Goldberg,Catabolin/interleukin-1 regulation of cartilage and chondrocyte metabolism. Agents and Actions21, 341–344 (1987).Google Scholar
- E. M. O'Byrne, V. Blancuzzi, D. E. Wilson, M. Wong and A. Y. Jeng,Blevated substance P and accelerated cartilage degradation in rabbit knees injected with interleukin-1 and tumor necrosis factor. Arth. Rheum.33, 1023–1028 (1990).Google Scholar
- J. Steinberg, S. Tsukamoto and C. B. Sledge,A tissue culture model of cartilage breakdown in rheumatoid arthritis. III. Effects of antirheumatic drugs. Arth. Rheum.22, 877–885 (1979).Google Scholar
- B. G. Steinetz, D. C. Swartzendruber, C. Colombo, M. Butler, E. O'Byrne, N. Wuerster and G. Lust,New parameters for evaluation of disease severity in a rabbit model of osteoarthritis. InAdvances in Inflammation Research. Vol. 11. (Ed. I. Otterness et al.) pp. 251–259, Raven Press, New York 1986.Google Scholar
- B. G. Steinetz, E. M. O'Byrne, M. C. Butler and L. B. Hickman,Hormonal regulation of the connective tissue of the symphysis pubis. InBiology of Relaxin and its Role in the Human. (Eds. M. Bigazzi, F. C. Greenwood and F. Gasparri) pp. 71–92, Excerpta Medica, Amsterdam, Oxford and Princeton 1983.Google Scholar
- B. G. Steinetz, R. L. Kroc and V. L. Beach,Bioassay of relaxin. InMethods in Hormone Research. (Ed. R. I. Dorfman) pp. 481–513 (1969).Google Scholar
- F. Kawamura,Effect of glycosaminoglycan-polysulfate on cartilage proteoglycans of experimentally produced osteoarthritis in rabbit knee joints. Nihon Univ. J. Med.23, 129–144 (1981).Google Scholar
- J. C. Golding and P. Ghosh,Drugs for osteoarthritis I: The effects of pentosan polysulfate (SP54) on the degradation and loss of proteoglycans from articular cartilage in a model of osteoarthrosis induced in the rabbit knee by immobilization. Current Therap. Res.33, 173–184 (1983).Google Scholar
- D. Howell, O. E. Muniz and M. R. Carreno,Effect of glycosaminoglycan polysulfate ester on proteoglycan-degrading enzyme activity in an animal model of osteoarthritis. InAdvances in Inflammation Research. Vol. 11. (Eds. I. Otterness et al.) pp. 197–205, Raven-Press, New York 1986.Google Scholar
- L. P. Yu, Jr., G. N. Smith, K. D. Brandt, S. L. Myers, B. L. O'Connor and D. A. Brandt,Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arth. Rheum.35, 1150–1159 (1992).Google Scholar
- M. Lingetti, P. L. D'Ambrosio, F. DiGrezia, P. Sorrentino and E. Lingetti,A controlled study in the treatment of osteoarthritis with diacetylrhein (Artrodar) Curr. Therap. Res.31, 408–412 (1982).Google Scholar
- C. Arsenis, R. A. Greenwald, A. Moak and R. S. Laskin,Inhibition of neutral metalloproteinase activities (MTP) in epiphyseal and articular cartilage by tetracyclines (TETS) both in vivo and in vitro. Trans. Orthop. Res. Soc.15, 268 (1990).Google Scholar
- M. Mian, D. Benetti, S. Rosini and R. Fantozzi,Rhein reduces proteoglycan loss during the autolytic breakdown of cultured cartilage. Int. J. Tiss. Reac.XI, 117–122 (1989).Google Scholar
- D. J. Buttle, C. J. Handley, M. Z. Ilic, J. Saklatvala, M. Murata and A. J. Barrett,Inhibition of cartilage proteoglycan release by a specific inactivator of cathepsin B and an inhibitor of matrix metalloproteinases. Evidence for two converging pathways of chondrocyte-mediated proteoglycan degradation. Arth. Rheum.36, 1709–1717 (1993).Google Scholar
- C. Colombo, M. Butler, L. Hickman, M. Selwyn, J. Chart and B. Steinetz,A new model of osteoarthritis in rabbits: II. Evaluation of antiosteoarthritic effects of selected antirheumatic drugs administered systemically. Arth. Rheum.26, 1132–1139 (1983).Google Scholar
- A. Weiss, E. Livne and M. Silbermann,Glucocorticoid hormone adversely affects the growth and regeneration of cartilage in vitro. Growth Develop. Aging52, 67–75 (1988).Google Scholar
- B. G. Steinetz, V. L. Beach and R. L. Kroc,The physiology of relaxin in laboratory animals. InRecent Progress in the Endocrinology of Reproduction. (Ed. C. H. Lloyd) pp. 389–423, Academic Press, New York and London 1959.Google Scholar