Rap1A Regulates Osteoblastic Differentiation via the ERK and p38 Mediated Signaling |
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| Authors: | Yougen Wu Juan Zhou Yinghua Li Yunjiao Zhou Yunqing Cui Gong Yang Yang Hong |
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| Affiliation: | 1. Central Laboratory, The Fifth People''s Hospital of Shanghai, Fudan University, Shanghai 200240, China.; 2. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.; 3. Department of Oncology, Fudan University Shanghai Medical College, Shanghai, 200032, China.; 4. Department of Osteology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China.; University of Texas Southwestern Medical Center, UNITED STATES, |
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| Abstract: | Rap1A is a member of small G proteins belonging to the Ras family. Recently, an integration of human genome-wide association studies (GWAS) and gene expression profiling study revealed that single-nucleotide polymorphisms (SNPs) within human Rap1A were strongly associated with narrow neck width in women. However, the regulatory role of Rap1A in osteoblasts remains to be elucidated. Here we report that Rap1A is a key regulator in osteoblast differentiation. Rap1A expression and activity were gradually enhanced during the induced differentiation of multipotent mesenchymal progenitor cells (C2C12) and preosteoblastic cells (MC3T3-E1). Knockdown of endogenous Rap1A significantly inhibited the osteogenic marker gene expression and matrix mineralization in cells with osteogenesis. In addition, knockdown of endogenous Rap1A suppressed the activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), while overexpression of Rap1A accelerated osteoblast differentiation and enhanced the phosphorylation of ERK and p38. Taken together, our study suggests that Rap1A regulates osteoblast differentiation through modulating the ERK/p38 signaling. |
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