LPS-stimulated inflammation inhibits BMP-9-induced osteoblastic differentiation through crosstalk between BMP/MAPK and Smad signaling

Experimental Cell Research
Lu DaigangZhang Kun

Abstract

Inflammation is a common situation during bone healing and is recognized to inhibit osteogenic differentiation and bone formation. However, the effect of inflammation on BMP-9-induced osteoblastic differentiation remains unclear. In the present study, we found that an inflammatory environment triggered by lipopolysaccharide (LPS) in vitro suppressed BMP-9-induced osteogenic differentiation. In addition, LPS decreased BMP-9-induced phosphorylation of Smad1/5/8 and showed obvious inhibitory effects on BMP-9-induced Smad signaling. We then confirmed that LPS and BMP-9 can activate p38MAPK and ERK1/2 signaling, and that LPS stimulation reduces BMP-9-induced Runx2 expression through the activation of p38MAPK and ERK1/2 signaling. Finally, we determined that blockade of MAPK signaling by specific inhibitors reverses the inhibitory effect of LPS on BMP-9-induced osteogenic differentiation, and that MAPK acts as a mediator of the negative regulatory role of LPS in BMP-9-induced activation of Smad signaling. Based on these results, we conclude that the LPS-mediated inflammatory environment inhibits BMP-9-induced osteogenic differentiation, via crosstalk between BMP/MAPK and Smad signaling. The elucidation of these mechanisms may hasten ...Continue Reading

References

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Citations

Sep 30, 2016·Cell Death & Disease·Zuozhang YangYa Zhang
Mar 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Di ZhuYan-Qiu Liu
Jun 8, 2017·Journal of Cellular Physiology·Maryam MajidiniaBahman Yousefi
Feb 10, 2018·Regenerative Biomaterials·Zhurong TangXingdong Zhang
Jan 2, 2020·International Journal of Molecular Sciences·Yiwen ZhangQiong Xu
Apr 20, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yanbei TuChengwei He
Jun 25, 2021·Journal of Ethnopharmacology·Xiaohan WeiXiaomei Tan

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