RRC ID 51749
Author Zhang Q, Matsui H, Horiuchi H, Liang X, Sasaki K.
Title A-Raf and C-Raf differentially regulate mechanobiological response of osteoblasts to guide mechanical stress-induced differentiation.
Journal Biochem Biophys Res Commun
Abstract Regulation of osteoblast activity by mechanical stress is important for bone remodeling. However, the precise mechanotransduction mechanism that triggers the anabolic reaction of osteoblasts is largely unknown. In this study, we performed RNA interference (RNAi) screening to identify the signaling molecules upstream of ERK, which was responsible for osteogenesis. Of twenty-two mitogen-activated protein kinase (MAPK) kinase kinases (MAP3Ks), we identified A-Raf and C-Raf as upstream MAP3Ks of the mechanical stretch-activated ERK pathway. Subsequently we screened the mechanosensitive cation channel, and identified P2X7 as an upstream molecule of the ERK pathway. Intriguingly, P2X7 functioned as an upstream activator of A-Raf but not of C-Raf. Furthermore, A-Raf contributed to mechanical stretch-induced osteoblast differentiation. In contrast, C-Raf but not A-Raf protected osteoblasts from mechanical stretch-induced apoptosis. These results suggested that A-Raf and C-Raf were involved in mechanobiological osteogenesis in a distinct way: A-Raf was responsible for osteogenesis while C-Raf for anti-apoptotic protection and promotion.
Volume 476(4)
Pages 438-444
Published 2016-8-5
DOI 10.1016/j.bbrc.2016.05.141
PII S0006-291X(16)30863-4
PMID 27240957
MeSH Animals Cell Differentiation / physiology Cell Line Cell Survival MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism Mice Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism Osteoblasts / cytology* Osteoblasts / physiology Proto-Oncogene Proteins A-raf / genetics Proto-Oncogene Proteins A-raf / metabolism* Proto-Oncogene Proteins c-raf / genetics Proto-Oncogene Proteins c-raf / metabolism* RNA Interference Receptors, Purinergic P2X7 / genetics Receptors, Purinergic P2X7 / metabolism Stress, Mechanical
IF 2.985
Times Cited 4
Human and Animal Cells MC3T3-E1(RCB1126)