title: PlexinA2 mediates osteoblast differentiation via regulation of Runx2.
abstract: The imbalance between bone-resorbing osteoclasts and bone-forming osteoblasts often leads to bone destructive diseases such as osteoporosis. In contrast to the development of several antiresorptive agents for osteoporosis therapy, discovery of anabolic drugs has been difficult because of an insufficient understanding of the complex mechanism of bone formation. In a microarray analysis with mouse preosteoblast cells, we found that PlexinA2 (PlxnA2), a molecule previously known to mediate axon guidance in neural development, was upregulated by the osteogenic factor BMP2. PlxnA2-specific siRNA decreased Runx2 expression, osteoblast differentiation, and mineralization. Runx2 overexpression restored osteoblastic differentiation of PlxnA2-knockdown cells. PlxnA2 was associated with both type 1 and 2 BMP receptors, and BMP2 increased the interaction between PlxnA2 and type 1 receptors. PlxnA2 also affected Smad and Akt signaling pathways downstream of BMP2. Taken together, the results of our study reveal that PlxnA2 has a pro-osteogenic function by modulating BMP2 signaling. Therefore, PlxnA2 may be a useful target for development of bone anabolic therapeutics.
authors.affiliation: Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Oh
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Woo-Shin
authors.initials: WS
authors.lastname: Kim
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Soon Jung
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology*; D017931:DNA Primers; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers; D009419:Nerve Tissue Proteins; C515995:PLXNA2 protein, human; C492113:Plxna2 protein, mouse; D034741:RNA, Small Interfering; C493709:RUNX2 protein, human; D011956:Receptors, Cell Surface; C493716:Runx2 protein, mouse