Home >> Expert Opinion on Therapeutic Targets, Volume 13, Number 1

Targeting bone morphogenetic protein antagonists: in vitro and in vivo evidence of their role in bone metabolism

Authors: Tsialogiannis, Evaggelos; Polyzois, Ioannis; Oak Tang, Quen; Pavlou, George; Tsiridis, Evgenios; Heliotis, Manolis; Tsiridis, Eleftherios

Source: Expert Opinion on Therapeutic Targets, Volume 13, Number 1, January 2009 , pp. 123-137(15)

Publisher: Informa Healthcare

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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. Results/conclusion: 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.
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