Regulation of Extra-cellular Matrix Metalloproteinase-3 (MMP-3 ) Promoter in mouse MC3T3-E1 cells under Cyclic Compression Force Stimulation
Date Issued
2010
Date
2010
Author(s)
Tsai, Shu-Chun
Abstract
The mechanism of bone remodeling by mechanical stimulation became an important issue in orthodontics recently. Previously, bone resorption in compression area during orthodontic treatment was found to be closely related to the expression of matrix metalloproteinases-3 (MMP-3), one of the members of matrix metalloproteinases family (MMPs). Also, the regulation of MMP-3 has been reported to be modified by mechanical compression in other portions of body, and involve bone resorption in arthritic joints and compressed intervertebrate discs. In order to verify how the mechanical compression may affect the MMP-3 gene expression, 1% cyclic compression force for 4, 8, 24 hours was applied to mouse osteoblast-like MC3T3-E1 cells grown in a 3D collagen gel to mimic the physiologic environment. The result of real-time PCR showed MMP-3 mRNA expression changed in a time-dependent manner, mild down-regulation at early times, but increased significantlty after 24 hour of compression, which was up-regulated for average 4.204-fold. In addition, luciferase activity of human MMP-3 promoter was also up-regulated average 4.62-fold in mouse MC3T3-E1 cells after 1%, 24 hours cyclic compression force. For identifying possible signaling pathways of MMP-3 promoter regulation, 5 inhibitors including MEK1/2 inhibitor (U0126)， p38 inhibitor (SB203580)，JNK II inhibitor (420128)，NF-κB inhibitor (BAY 11-7082)，PI3-K inhibitor (LY 29400) were tested. The dual luciferase ananlysis showed that p38 inhibitor (SB203580)和PI3-K inhibitor (LY 29400) both had down-regulated MMP-3 promoter. Thus we concluded that MMP-3 gene expression in mouse MC3T3-E1 cells was up-regulated by 1%, 24 hours cyclic compression, and so was the transfected human MMP-3 promoter. And the p38和PI3-K pathways possibly involved for the mechanical stimulated expresssion of MMP-3 promoter.
Subjects
matrix metalloproteinase
mechanical stress
MC3T3-E1 osteoblast
Type
thesis
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