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Stretch‐induced modulation of matrix metalloproteinases in mineralizing osteoblasts via extracellular signal‐regulated kinase‐1/2
Author(s) -
Jansen Justus H.,
Jahr Holger,
Verhaar Jan A.N.,
Pols Huib A.P.,
Chiba H.,
Weinans Harrie,
van Leeuwen Johannes P.T.M.
Publication year - 2006
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20186
Subject(s) - matrix metalloproteinase , extracellular matrix , modulation (music) , microbiology and biotechnology , chemistry , kinase , matrix (chemical analysis) , signal (programming language) , extracellular , signal transduction , biophysics , materials science , biology , biochemistry , physics , computer science , acoustics , chromatography , programming language
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) produced by osteoblasts play an essential role in bone remodeling. Hence, these proteins could provide an interesting means by which mechanical loading leads to adaptation of bone. Here, we examined the effect of stretch on MMP‐1, ‐2, ‐3, ‐8, ‐9, ‐13, and ‐14, as well as TIMP‐1 and ‐2 gene expression in differentiating, mineralizing, and nonmineralizing human SV‐40 immortalized preosteoblast cells. In the mineralizing osteoblast culture, but not in the nonmineralizing cultures, cyclic stretch for only 15 min resulted in an increase of MMP‐1 (fourfold) and ‐3 (depending on differentiation stage up to 25‐fold) transcript abundance. No clear effect was observed for other MMPs, TIMP‐1 or ‐2. The increase of MMP‐1 and ‐3 was confirmed on the protein level. Stretching experiments performed in the presence of a specific inhibitor of extracellular signal‐regulated kinase (ERK) showed a strong suppression of the stretch‐induced increase in MMP‐1 and ‐3. In conclusion, we show that MMP‐1 and MMP‐3 are mechanosensitive genes in mineralizing the human osteoblast, and that the mechano‐induction of these genes is mediated via the ERK pathway. Our findings implicate that these MMPs are important factors in the mechanoregulation of bone turnover. With the ability to generate MMPs at highly stretched sites, osteoblasts can potantially direct osteoclasts to specific bone surface areas prepared for resorption. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1480–1488, 2006