Nmp4/CIZ contributes to fluid shear stress induced MMP-13 gene induction in osteoblasts

Kanokwan Charoonpatrapong-Panyayong, Rita Shah, Jieping Yang, Marta Alvarez, Fredrick M. Pavalko, Rita Gerard-O'Riley, Alexander G. Robling, Evan Templeton, Joseph P. Bidwell

Research output: Contribution to journalArticle

19 Scopus citations


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 p130cas, 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/cm2, 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 p130cas 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.

Original languageEnglish (US)
Pages (from-to)1202-1213
Number of pages12
JournalJournal of Cellular Biochemistry
Issue number5
StatePublished - Dec 1 2007


  • Bone
  • Mechanical load
  • Mechanosome
  • Mechanotransduction
  • p130

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Nmp4/CIZ contributes to fluid shear stress induced MMP-13 gene induction in osteoblasts'. Together they form a unique fingerprint.

  • Cite this