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Nmp4/CIZ contributes to fluid shear stress induced MMP‐13 gene induction in osteoblasts
Author(s) -
CharoonpatrapongPanyayong Kanokwan,
Shah Rita,
Yang Jieping,
Alvarez Marta,
Pavalko Fredrick M.,
GerardO'Riley Rita,
Robling Alexander G.,
Templeton Evan,
Bidwell Joseph P.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21349
Subject(s) - osteoblast , transcription factor , microbiology and biotechnology , transcription (linguistics) , runx2 , matrix metalloproteinase , zinc finger , chemistry , biology , gene , biochemistry , in vitro , linguistics , philosophy
The expression of matrix metalloproteinase‐13 (MMP‐13), involved in bone turnover, is elevated in stretched MC3T3‐E1 osteoblast‐like cells. Strain‐mediated forces impact bone remodeling due in large part to the movement of fluid through the canalicular‐lacunar network. The resulting fluid shear stress (FSS) over the surface membranes of bone cells initiates bone remodeling. Although the nuclear events mediating putative FSS‐induced changes in osteoblast MMP‐13 transcription are unknown, previous studies with bone cells suggest an overlap between osteoblast FSS‐ and PTH‐induced signal response pathways. MMP‐13 PTH response is regulated by a 110 bp 5′ regulatory region, conserved across the mouse, rat, and human genes, that supports the binding of numerous transcription factors including Runx2, c‐fos/c‐jun, Ets‐1, and nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) a nucleocytoplasmic shuttling trans‐acting protein that attenuates PTH‐driven transcription. Nmp4/CIZ also binds p130 cas , an adaptor protein implicated in mechanotransduction. Here we sought to determine whether Nmp4/CIZ contributes to FSS‐induced changes in MMP‐13 transcription. FSS (12 dynes/cm 2 , 3–5 h) increased MMP‐13 promoter‐reporter activity approximately two‐fold in MC3T3‐E1 osteoblast‐like cells attended by a comparable increase in mRNA expression. This was accompanied by a decrease in Nmp4/CIZ binding to its cis‐element within the PTH response region, the mutation of which abrogated the MMP‐13 response to FSS. Interestingly, FSS enhanced Nmp4/CIZ promoter activity and induced p130 cas nuclear translocation. We conclude that the PTH regulatory region of MMP‐13 also contributes to FSS response and that Nmp4/CIZ plays similar but distinct roles in mediating hormone‐ and FSS‐driven induction of MMP‐13 in bone cells. J. Cell. Biochem. 102: 1202–1213, 2007. © 2007 Wiley‐Liss, Inc.