Targeting bone morphogenetic protein antagonists: in vitro and in vivo evidence of their role in bone metabolism.
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.
Tsialogiannis
Evaggelos
E
Clinical and Research Fellow Leeds School of Medicine, Academic Orthopaedic Unit, Leeds General Infirmary, Leeds, UK.
Polyzois
Ioannis
I
Oak Tang
Quen
Q
Pavlou
George
G
Tsiridis
Evgenios
E
Heliotis
Manolis
M
Tsiridis
Eleftherios
E
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D001842:Bone and Bones / Q000378:metabolism*; D006801:Humans; D051379:Mice
D019485:Bone Morphogenetic Proteins