Authors: Liang Wang Jianyu Li Xizheng Zhang Lu Liu Zongming Wan Ruixin Li Yong Guo
Publish Date: 2012/03/23
Volume: 40, Issue: 9, Pages: 1884-1894
Abstract
Bone morphogenetic proteins BMPs are known to be important in osteoblasts’ response to mechanical stimuli BMPs/Smad signaling pathway has been demonstrated to play a regulatory role in the mechanical signal transduction in osteoblasts However little is currently known about the Smad independent pathway in osteoblasts differentiation in mechanical loading In this study MC3T3E1 cells were subjected to mechanical stretch of 2000 microstain με at 05 Hz in order to investigate the involvement of p38MAPK and NFκB signaling pathways in mechanical response in osteoblasts We found BMP2/BMP4 were upregulated by mechanical stretch via the earlier activation of p38MAPK and NFκB signaling pathways which enhanced osteogenic gene expressions including alkaline phosphatase ALP collagen type I Col I and osteocalcin OCN and the expressions of these osteogenic genes were remarkably decreased with Noggin an inhibitor for BMPs signals pretreatment Furthermore BMP2/BMP4 expressions were suppressed by PDTC an inhibitor of NFκB pathway and SB203580 an inhibitor of p38MAPK pathway respectively leading to the declined levels of ALP Col I and OCN Interestingly blocking in p38MAPK pathway can also cause the inactivation of NFκB pathway in mechanical stretch Collectively the results indicate during mechanical stretch p38MAPK and NFκB signaling pathways are activated first and then upregulate BMP2/BMP4 to enhance osteogenic gene expressions Moreover p38MAPK and NFκB signals have crosstalk in regulation of BMP2/BMP4 in mechanical response
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