The Downstream RAF-1 Signaling Of Fibroblast Growth Factor-23 Participates In The Osteogenetic Effect Caused By C-type Natriuretic Peptide In Vitro

Background: Since the effects of fibroblast growth factor(FGF)-23 and C-type natriuretic peptide(CNP)on bone formation appear to oppose each other,it is reasonable to hypothesize that several intracellular signaling pathways,such as mitogen-activated protein kinase(MAPK),may participate in their cross-actions.Several studies have demonstrated that CNP stimulates osteoblastic proliferation seemly via antagonizing the expression of FGF-23 in vitro.The main aim of the present study is to probe whether the post-receptor pathways of FGF-23 participate in osteogenesis caused by CNP.Methods: Osteoblasts were cultured in the absence or presence of CNP: 0,10,and 100pmol/L,for 24 h,48 h and 72 h,respectively.Results: The findings of the present study indicated that osteoblastic proliferation was directly promoted by exogenous CNP in a dose-dependent manner;osteoblastic FGF-23 was significantly down-regulated by CNP at 24 h post-treatment;RAF-1,extracellular signalregulated kinases(ERK),and P38 were substantially suppressed by CNP in a dose-and timedependent manner;and signal transducer and activator of transcription(STAT)-1 was not changed on the premise of the down-regulated FGF-23 in osteoblasts treated with CNP.Conclusions: CNP may promote osteogenesis via inhibiting ERK and P38,rather than STAT-1,in the downstream of FGF-23/RAF-1 pathway.