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.
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.
Authors: Adil Akkouch; Steven Eliason; Mason E Sweat; Miguel Romero-Bustillos; Min Zhu; Fang Qian; Brad A Amendt; Liu Hong Journal: Hum Gene Ther Date: 2019-08-16 Impact factor: 5.695
Authors: Suzanne N Lissenberg-Thunnissen; David J J de Gorter; Cornelis F M Sier; Inger B Schipper Journal: Int Orthop Date: 2011-06-23 Impact factor: 3.075
Authors: Mohamed Al-Shabrawey; Khaled Hussein; Fang Wang; Ming Wan; Khaled Elmasry; Nehal Elsherbiny; Heba Saleh; Paul B Yu; Amany Tawfik; Ahmed S Ibrahim Journal: Front Immunol Date: 2021-01-29 Impact factor: 8.786