title: [Tenascin-C knockdown suppresses osteoblast differentiation and promotes osteoporosis in mice by inhibiting Wnt signaling].
abstract: OBJECTIVE
  To understand the mechanism by which tenascin-C regulates osteoblast differentiation and the role of tenascin-C in osteoporosis.
  
  
  METHODS
  Tenascin-C protein expression in femoral spongy bone of mice with or without osteoporosis was analyzed using Western blotting. In MC3T3-E1 osteoblasts with or without tenascin-C depletion by a specific siRNA targeting tenascin-C, alkaline phosphatase activity and Dickkopf-1 (DKK-1) expression were determined using quantitative RT-PCR and Western blotting, and the transcriptional activity of Wnt signaling pathway was analyzed using a luciferase reporter assay. The possible interaction of tenascin-C with DKK-1 predicted by STRING software was verified by immunoprecipitation.
  
  
  RESULTS
  s Tenascin-C was markedly down-regulated in hemoral spongy bone of mice with osteoporosis as compared with the control mice. Osteoblastic differentiation was markedly suppressed in MC3T3-E1 osteoblast after tenascin-C depletion, and was significantly reversed by simultaneous β-catenin over-expression. siRNA-mediated knockdown of tenascin-C, which bound DKK-1, up-regulated the expression of DKK-1 and consequently lowered the transcriptional activity of Wnt pathway.
  
  
  CONCLUSIONS
  Tenascin-C knockdown attenuates its negative control on DKK-1 to suppress the transcriptional activity of Wnt pathway, which in turn suppresses osteoblastic differentiation and promotes osteoporosis.
authors: Department of Orthopedics, South Branch of Fujian Provincial Hospital, Fuzhou 350001, China. E-mail: hefan1977@126.com.
authors: Yu
authors: Y
authors: Chen
authors: Zi-Feng
authors: ZF
authors: Chen
authors: Fan
authors: F
authors: He
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D055785:Gene Knockdown Techniques; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis; D010024:Osteoporosis / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000235:genetics; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D019063:Tenascin; D051176:beta Catenin