Document Detail

Role of MT1-MMP in the osteogenic differentiation.
MedLine Citation:
PMID:  19027888     Owner:  NLM     Status:  MEDLINE    
Metalloproteinase MT1-MMP is induced and Pro-MMP-2 up modulated early in rat preosteoblasts (ROB) set to differentiate. We here show that the induction of MMPs, accompanied by activation of Pro-MMP-2, occurs by 6 h of adhesion on endogenous extracellular matrix (ECM), Fibronectin (FN) and Collagen type I (CI). These events do not occur after adhesion on Collagen III (CIII), Vitronectin (VN) or BSA. Within the first hour on inducing substrata or plastic, FAK is unchanged and ERK(1,2), is activated, but this activation is not sufficient for MT1-MMP induction. The function of p38 MAPK and PTKs is not required for the induction by substrata of MMPs. Six hours after plating preosteoblasts on MMP-inducing substrata, complexes of beta1 integrin with MT1-MMP are formed, that contain integrin dimers specifically engaged by the substratum, alpha4 and alpha5 chains for cells plated on FN, and alpha2 chain for cells plated on CI and ECM. Induction of MT1-MMP and its expression during osteogenesis pleiotropically regulate alkaline phosphatase (AP) expression. During differentiation, variant clones derived from preosteoblasts and MMPs-over-expressing osteoblasts show high MT1-MMP level associated with high AP level both persisting in time, while inhibition of MMPs is accompanied by inhibition of AP. Up or down modulation of AP, transcriptionally or by inhibition of the enzyme activity, has no effect on level or timing of expression of MT1-MMP and Pro-MMP-2. The persistence in expression of MT1-MMP during differentiation, and the associated persistence in expression of AP, as well as their inhibition, both impair the formation of nodules and mineral deposition. A transient pattern of expression of MT1-MMP is required for the establishment of nodules, and MT1-MMP decrease is permissive for nodule mineralization. The expression of AP is required for nodule formation and its level modulates the mineralization. MT1-MMP has multiple functions and is implicated in multiple steps of the differentiation process, acting to regulate homeostasis of the osteogenic differentiation.
Paola Manduca; Alessia Castagnino; Domenico Lombardini; Stefania Marchisio; Stefano Soldano; Valentina Ulivi; Stefano Zanotti; Corrado Garbi; Nicoletta Ferrari; Daniela Palmieri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-05
Journal Detail:
Title:  Bone     Volume:  44     ISSN:  1873-2763     ISO Abbreviation:  Bone     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-26     Completed Date:  2009-03-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  251-65     Citation Subset:  IM    
Genetics, DiBio, University of Genoa, 26, C. Europa, Genoa 16132, Italy.
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MeSH Terms
Alkaline Phosphatase / metabolism
Antigens, CD29 / metabolism
Calcification, Physiologic / drug effects
Calcium / metabolism
Cell Differentiation* / drug effects
Cell Separation
Clone Cells
Collagen Type I / pharmacology
Enzyme Inhibitors / pharmacology
Extracellular Matrix / metabolism
Fibronectins / pharmacology
Matrix Metalloproteinase 14 / antagonists & inhibitors,  metabolism*
Osteoblasts / cytology*,  drug effects,  enzymology*
Osteogenesis* / drug effects
Protein Multimerization / drug effects
Protein-Tyrosine Kinases / metabolism
Signal Transduction / drug effects
Staining and Labeling
Talin / metabolism
Reg. No./Substance:
0/Antigens, CD29; 0/Collagen Type I; 0/Enzyme Inhibitors; 0/Fibronectins; 0/Talin; 7440-70-2/Calcium; EC Kinases; EC Phosphatase; EC Metalloproteinase 14

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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