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Regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by bone resorptive factors in osteoblastic cells
Author(s) -
Uchida Motoyuki,
Shima Masaaki,
Shimoaka Takashi,
Fujieda Ayako,
Obara Kazumi,
Suzuki Hiroyuki,
Nagai Yumiko,
Ikeda Toshiyuki,
Yamato Hideyuki,
Kawaguchi Hiroshi
Publication year - 2000
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(200011)185:2<207::aid-jcp5>3.0.co;2-j
Subject(s) - matrix metalloproteinase , bone resorption , endocrinology , chemistry , medicine , parathyroid hormone , microbiology and biotechnology , bone cell , bone remodeling , biology , calcium
In addition to their stimulating function on osteoclastic bone resorption, bone resorptive factors may regulate proteinases and related factors in osteoblastic cells to degrade bone matrix proteins. This study investigated the regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by bone resorptive factors in the cultures of mouse osteoblastic MC3T3‐E1 cells, mouse primary osteoblastic (POB) cells, and neonatal mouse calvariae. Expression of either MMP‐2, ‐3, ‐9, ‐11, ‐13, and ‐14 or TIMP‐1, ‐2, and ‐3 was detected in MC3T3‐E1 cells and POB cells. When the bone resorptive factors parathyroid hormone, 1,25‐dihydroxyvitamin D 3 , prostaglandin E 2 , interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) were added to the cell cultures, MMP‐13 mRNA levels were found predominantly to increase by all resorptive factors in the three cultures. mRNA levels of either MMP‐3 and ‐9 or TIMP‐1 and ‐3 were found to increase mainly by the cytokines IL‐1β and TNF‐α. BB94, a nonselective MMP inhibitor, neutralized the 45 Ca release stimulated by these resorptive factors to an extent similar to that of calcitonin, strongly suggesting that bone resorptive factors function at least partly through MMP formation. We propose that MMP‐13 mRNA expression in osteoblastic cells may play an important role in stimulating matrix degradation by both systemic and local resorptive factors, whereas either MMP‐3 and ‐9 or TIMP‐1 and ‐3 might modulate matrix degradation by local cytokines only. J. Cell. Physiol. 185:207–214, 2000. © 2000 Wiley‐Liss, Inc.