title: Rap1A Regulates Osteoblastic Differentiation via the ERK and p38 Mediated Signaling.
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.
authors.affiliation: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Yougen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Fudan University Shanghai Medical College, Shanghai, 200032, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.|Department of Osteology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020827:rap1 GTP-Binding Proteins