LPS-stimulated inflammation inhibits BMP-9-induced osteoblastic differentiation through crosstalk between BMP/MAPK and Smad signaling.
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 the development of new strategies and improve the osteoinductive efficacy of BMP-9 in the clinic, resulting in enhanced osteoblastic differentiation and bone formation.
['Daigang|Lu|L|', 'Jining|Qu|Q|', 'Jinlai|Lei|L|', 'Pengfei|Wang|W|', 'Chuan|Sun|S|', 'Liangku|Huang|H|', 'Ding|Tian|T|', 'Zhe|Song|S|', 'Wei|Wei|W|', 'Zhong|Li|L|', 'Kun|Zhang|Z|']
D000818:Animals D002454:Cell Differentiation D055427:Growth Differentiation Factor 2 D007249:Inflammation D008070:Lipopolysaccharides D051379:Mice D010006:Osteoblasts D015398:Signal Transduction D051785:Smad Proteins D048051:p38 Mitogen-Activated Protein Kinases
Osteogenic differentiation LPS BMP-9