title: Targeting bone morphogenetic protein antagonists: in vitro and in vivo evidence of their role in bone metabolism.
abstract: BACKGROUND
  Bone morphogenetic proteins (BMPs) and their antagonists are involved in fracture healing. Antagonists regulate BMPs by blocking signal transduction or interfering with transcription factors at the nucleus.
  
  
  OBJECTIVE
  To examine targeting of BMP antagonists to manipulate osteogenesis.
  
  
  METHODS
  An overview of in vitro and in vivo evidence on effects of BMP antagonists on bone metabolism.
  
  
  CONCLUSIONS
  There is in vitro evidence suggesting that overexpression of noggin and gremlin inhibits osteogenic differentiation, markedly decreases alkaline phosphatase (ALP) levels and impedes R-Smad (1/5/8) phosphorylation in murine cell lines. Knockdown of chordin results in a threefold increase in ALP activity in human mesenchymal stem cells. In vivo data shows that inhibition of noggin leads to increased bone regeneration in mice. Noggin and sclerostin can combine in a mutually inhibitory complex, neutralising their individual inhibitory effects. This allows BMP signalling to proceed to osteoinduction. We highlight the potential for clinical enhancement of bone formation through inhibition of BMP antagonists.
authors.affiliation: Clinical and Research Fellow Leeds School of Medicine, Academic Orthopaedic Unit, Leeds General Infirmary, Leeds, UK.
authors.forename: Evaggelos
authors.initials: E
authors.lastname: Tsialogiannis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Polyzois
authors.forename: Quen
authors.initials: Q
authors.lastname: Oak Tang
authors.forename: George
authors.initials: G
authors.lastname: Pavlou
authors.forename: Evgenios
authors.initials: E
authors.lastname: Tsiridis
authors.forename: Manolis
authors.initials: M
authors.lastname: Heliotis
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Tsiridis
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D001842:Bone and Bones / Q000378:metabolism*; D006801:Humans; D051379:Mice
chemical_list: D019485:Bone Morphogenetic Proteins