Regulation of Matrix Metalloproteinases (MMP-2, -3, -9, and -13) by Interleukin-1 and Interleukin-6 in Mouse Calvaria: Association of MMP Induction with Bone Resorption* (original) (raw)

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1Department of Biochemistry (Ke.K., C.M., M.I., T.T., T.S.), School of Dentistry, Showa University, Tokyo 142, Japan

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1Department of Biochemistry (Ke.K., C.M., M.I., T.T., T.S.), School of Dentistry, Showa University, Tokyo 142, Japan

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1Department of Biochemistry (Ke.K., C.M., M.I., T.T., T.S.), School of Dentistry, Showa University, Tokyo 142, Japan

5Department of Periodontology (M.I., Ky.K.), School of Dentistry at Tokyo, Nippon Dental University, Tokyo, 102, Japan

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1Department of Biochemistry (Ke.K., C.M., M.I., T.T., T.S.), School of Dentistry, Showa University, Tokyo 142, Japan

2Fuji Gotemba Research Laboratories (T.T.), Chugai Pharmaceutical Company, Ltd., Shizuoka 412, Japan

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3Department of Biochemistry (A.I.), School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, 192–03, Japan

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4Department of Biochemistry and Molecular Biology (H.N.), University of Kansas Medical Center, Kansas City, Kansas 66160

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5Department of Periodontology (M.I., Ky.K.), School of Dentistry at Tokyo, Nippon Dental University, Tokyo, 102, Japan

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1Department of Biochemistry (Ke.K., C.M., M.I., T.T., T.S.), School of Dentistry, Showa University, Tokyo 142, Japan

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04 September 1997

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Kenichiro Kusano, Chisato Miyaura, Masaki Inada, Tatsuya Tamura, Akira Ito, Hideaki Nagase, Kyuichi Kamoi, Tatsuo Suda, Regulation of Matrix Metalloproteinases (MMP-2, -3, -9, and -13) by Interleukin-1 and Interleukin-6 in Mouse Calvaria: Association of MMP Induction with Bone Resorption, Endocrinology, Volume 139, Issue 3, 1 March 1998, Pages 1338–1345, https://doi.org/10.1210/endo.139.3.5818
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Interleukin-1 (IL-1) greatly induces osteoclast formation and stimulates bone resorption of mouse calvaria in culture. In the presence of soluble IL-6 receptor (sIL-6R), IL-6 similarly induces osteoclast formation, but the potency of IL-6 in inducing bone resorption in organ culture is weaker than that of IL-1. To study the differences in bone-resorbing activity between IL-1 and IL-6, we examined the effects of the two cytokines on the induction of matrix metalloproteinases (MMPs). In mouse calvarial cultures, IL-1 markedly enhanced the messenger RNA (mRNA) expression of MMP-13 (collagenase 3), MMP-2 (gelatinase A), MMP-9 (gelatinase B), and MMP-3 (stromelysin 1), which associated with increases in bone matrix degradation. A hydroxamate inhibitor of MMPs significantly suppressed bone-resorbing activity induced by IL-1. Gelatin zymography showed that both pro- and active-forms of MMP-2 and MMP-9 were detected in the conditioned medium collected from calvarial cultures, and IL-1 markedly stimulated both pro- and active-forms of the two gelatinases. IL-6 with sIL-6R also stimulated mRNA expression and biological activities of these MMPs, but the potency was much weaker than that of IL-1. Conditioned medium collected from IL-1-treated calvariae degraded native type I collagen, but 3/4- and 1/4-length collagen fragments were not detected, suggesting that both collagenases and gelatinases synergistically degraded type I collagen into smaller fragments. In mouse osteoblastic cells, the expression of MMP-2, MMP-3, and MMP-13 mRNAs could be detected, and they were markedly enhanced by IL-1α on days 2 and 5. IL-6 with sIL-6R also induced expression of MMP-13 and MMP-2 mRNAs on day 2, but the expression was rather transient. These results demonstrate that the potency of induction of MMPs by IL-1 and IL-6 is closely linked to the respective bone-resorbing activity, suggesting that MMP-dependent degradation of bone matrix plays a key role in bone resorption induced by these cytokines.

Copyright © 1998 by The Endocrine Society

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