Opposing TNF-α/IL-1β- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation.

ABSTRACT: In patients who were treated with exogenous BMP-2 to repair bone fractures or defects, the levels of the inflammatory cytokines such as TNF-α and IL-1β in sera are significantly elevated, which may affect the outcome of bone regeneration. Mitogen-activated protein kinase (MAPK) cascades such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun NH2-terminal kinase 1/2 (JNK1/2) have a crucial role in osteogenic differentiation and are activated by both BMP-2 and TNF-α/IL-1β. However, previous studies suggested that the effects of BMP-2 and TNF-α/IL-1β in osteoblastic differentiation are opposite. Here, we investigated the exact role of MAPKs in a BMP-2 and TNF-α/IL-1β co-existed condition. Treatment with TNF-α/IL-1β inhibited BMP-2-induced alkaline phosphatase activity, calc

SUBMITTER: Huang RL 

PROVIDER: S-EPMC4001295 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature