title: Distribution, gene expression, and functional role of EphA4 during ossification.
abstract: EphA4 receptor tyrosine kinase has been shown to be critically involved in neural tissue development. Here, we found EphA4 was also distributed among hypertrophic chondrocytes and osteoblasts in the growth plate of developing mouse long bones. In vitro evaluation revealed that ephA4 expression was elevated upon hypertrophic differentiation of chondrocytes and that markedly stronger expression was observed in osteoblastic SaOS-2 than chondrocytic HCS-2/8 cells. Of note, RNAi-mediated silencing of ephA4 in SaOS-2 cells resulted in the repression of osteocalcin gene expression and alkaline phosphatase activity. Interestingly, confocal laser-scanning microscopic analysis revealed the presence of EphA4 molecules in the nucleus as well as on the surface of SaOS-2 cells. These findings are the first indication of a critical role of EphA4 in ossification, especially at the final stage in which osteoblasts and hypertrophic chondrocytes play major roles.
authors.affiliation: Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Kuroda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubota
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kawata
authors.forename: Eriko
authors.initials: E
authors.lastname: Aoyama
authors.forename: Kumi
authors.initials: K
authors.lastname: Sumiyoshi
authors.forename: Morihiko
authors.initials: M
authors.lastname: Oka
authors.forename: Miho
authors.initials: M
authors.lastname: Inoue
authors.forename: Shogo
authors.initials: S
authors.lastname: Minagi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takigawa
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000201:enzymology*; D015870:Gene Expression; D006132:Growth Plate / Q000201:enzymology* / Q000254:growth & development; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000201:enzymology*; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D015675:Osteocalcin; D036122:Receptor, EphA4; D000469:Alkaline Phosphatase