Key Points
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Phylogenetic analysis indicates that the bone morphogenetic protein (BMP) pathway is ancient and highly conserved across the animal kingdom
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Gene duplication and divergence has created a diverse matrix of BMP ligand–receptor pairs that achieve sophisticated control of signalling through variable activity profiles and functional redundancy
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Members of the BMP superfamily affect almost all aspects of bone, cartilage and joint biology
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Altered BMP signalling is a major underlying cause of human skeletal disorders
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Modulation of BMP signalling is emerging as a promising therapeutic strategy for improving bone mass and bone quality, ameliorating diseases of skeletal overgrowth and repairing damage to bones and joints
Abstract
Since the identification in 1988 of bone morphogenetic protein 2 (BMP2) as a potent inducer of bone and cartilage formation, BMP superfamily signalling has become one of the most heavily investigated topics in vertebrate skeletal biology. Whereas a large part of this research has focused on the roles of BMP2, BMP4 and BMP7 in the formation and repair of endochondral bone, a large number of BMP superfamily molecules have now been implicated in almost all aspects of bone, cartilage and joint biology. As modulating BMP signalling is currently a major therapeutic target, our rapidly expanding knowledge of how BMP superfamily signalling affects most tissue types of the skeletal system creates enormous potential to translate basic research findings into successful clinical therapies that improve bone mass or quality, ameliorate diseases of skeletal overgrowth, and repair damage to bone and joints. This Review examines the genetic evidence implicating BMP superfamily signalling in vertebrate bone and joint development, discusses a selection of human skeletal disorders associated with altered BMP signalling and summarizes the status of modulating the BMP pathway as a therapeutic target for skeletal trauma and disease.
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Acknowledgements
The authors would like to thank S. Pregizer and all members of the Rosen Lab for ideas, constructive comments and support during the assembly of this Review. The authors have made every attempt to be comprehensive in citing studies relevant to the objectives of this manuscript and apologize for any possible oversights or omissions made for the sake of space constraints.
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V.S.S., L.W.G and V.R. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.
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Supplementary information
Supplementary information S1 (table)
Experimental genetics of BMP pathway ligands in murine skeletal development. (PDF 172 kb)
Supplementary information S2 (table)
Experimental genetics of BMP pathway type I receptors in murine skeletal development. (PDF 141 kb)
Supplementary information S3 (table)
Experimental genetics of BMP pathway type II receptors in murine skeletal development. (PDF 117 kb)
Supplementary information S4 (table)
Experimental genetics of BMP pathway SMADs in murine skeletal development. (PDF 118 kb)
Supplementary information S5 (table)
Experimental genetics of BMP pathway secreted antagonists in murine skeletal development. (PDF 99 kb)
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Salazar, V., Gamer, L. & Rosen, V. BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol 12, 203–221 (2016). https://doi.org/10.1038/nrendo.2016.12
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DOI: https://doi.org/10.1038/nrendo.2016.12
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