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Involvement of p38MAPK/NF-κB Signaling Pathways in Osteoblasts Differentiation in Response to Mechanical Stretch

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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, MC3T3-E1 cells were subjected to mechanical stretch of 2000 micro-stain (με) at 0.5 Hz, in order to investigate the involvement of p38MAPK and NF-κB signaling pathways in mechanical response in osteoblasts. We found BMP-2/BMP-4 were up-regulated by mechanical stretch via the earlier activation of p38MAPK and NF-κB 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, BMP-2/BMP-4 expressions were suppressed by PDTC, an inhibitor of NF-κB 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 NF-κB pathway in mechanical stretch. Collectively, the results indicate during mechanical stretch p38MAPK and NF-κB signaling pathways are activated first, and then up-regulate BMP-2/BMP-4 to enhance osteogenic gene expressions. Moreover, p38MAPK and NF-κB signals have cross-talk in regulation of BMP-2/BMP-4 in mechanical response.

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Acknowledgments

This work was supported by grants from the National Nature Science Foundation of China (No. 10832012).

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All the authors certify that they have no financial and personal relationship that could inappropriately influence or bias this work.

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Authors and Affiliations

  1. Tianjin Institute of Medical Equipment, No. 106 Wandong Road, Hedong District, Tianjin, 300161, China

    Liang Wang, Jian-yu Li, Xi-zheng Zhang, Lu Liu, Zong-ming Wan, Rui-xin Li & Yong Guo

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  1. Liang Wang
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Correspondence to Xi-zheng Zhang.

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Associate Editor Kent Leach oversaw the review of this article.

Liang Wang and Jian-yu Li contributed equally to this work.

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Wang, L., Li, Jy., Zhang, Xz. et al. Involvement of p38MAPK/NF-κB Signaling Pathways in Osteoblasts Differentiation in Response to Mechanical Stretch. Ann Biomed Eng 40, 1884–1894 (2012). https://doi.org/10.1007/s10439-012-0548-x

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