BMP signalling in skeletal development, disease and repair

wbldb

Salazar, Valerie S.¹; Gamer, Laura W.¹; Rosen, Vicki¹

BMP signalling in skeletal development, disease and repair

Nat Rev Endocrinol. April 2016;12(4):203-221

©2016 Macmillan Publishers Limited. All rights reserved.

Affiliations

¹Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, Massachusetts 02115, USA
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.
Links

DOI: 10.1038/nrendo.2016.12

PubMed: 26893264

WoS: 000372858300004
History

Online: 2016-02-19

Cited Works (8)

Year	Entry
2009	Colnot C. Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration. J Bone Miner Res. February 2009;24(2):274-282.
2014	Zhou X, von der Mark K, Henry S, Norton W, Adams H, de Crombrugghe B. Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet. December 2014;10(12):e1004820.
2006	Rodda SJ, McMahon AP. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development. August 15, 2006;133(16):3231-3244.
1996	Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabi CJ. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science. August 2, 1996;273(5275):613-622.
1988	Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA. Novel regulators of bone formation: molecular clones and activities. Science. December 16, 1988;242(4885):1528-1534.
2006	Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho T-J, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. May 2006;38(5):525-528.
2014	Yang L, Tsang KY, Tang HC, Chan D, Cheah KSE. Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc Natl Acad Sci USA. August 19, 2014;111(33):12097-12102.
2006	Tsuji K, Bandyopadhyay A, Harfe BD, Cox K, Kakar S, Gerstenfeld L, Einhorn T, Tabin CJ, Rosen V. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet. December 2006;38(12):1424-1429.

Cited By (18)

Year	Entry
2020	Lukač N, Katavić V, Novak S, Šućur A, Filipović M, Kalajzić I, Grčević D, Kovačić N. What do we know about bone morphogenetic proteins and osteochondroprogenitors in inflammatory conditions? Bone. August 2020;137:115403.
2020	Wang W, Rigueur D, Lyons KM. TGFβ as a gatekeeper of BMP action in the developing growth plate. Bone. August 2020;137:115439.
2020	Yang J, Ueharu H, Mishina Y. Energy metabolism: a newly emerging target of BMP signaling in bone homeostasis. Bone. September 2020;138:115467.
2020	Mendes LF, Bosmans K, Van Hoven I, Viseu SR, Maréchal M, Luyten FP. Developmental engineering of living implants for deep osteochondral joint surface defects. Bone. October 2020;139:115520.
2020	Sampath TK, Vukicevic S. Biology of bone morphogenetic protein in bone repair and regeneration: a role for autologous blood coagulum as carrier. Bone. December 2020;141:115602.
2020	Migliorini E, Guevara-Garcia A, Albiges-Rizo C, Picart C. Learning from BMPs and their biophysical extracellular matrix microenvironment for biomaterial design. Bone. December 2020;141:115540.
2021	Long F, Shi H, Li P, Guo S, Ma Y, Wei S, Li Y, Gao F, Gao S, Wang M, Duan R, Wang X, Yang K, Sun W, Li X, Li J, Liu Q. A SMOC2 variant inhibits BMP signaling by competitively binding to BMPR1B and causes growth plate defects. Bone. January 2021;142:115686.
2021	Samsa WE, Mamidi MK, Hausman BS, Bashur LA, Greenfield EM, Zhou G. The master developmental regulator Jab1/Cops5/Csn5 is essential for proper bone growth and survival in mice. Bone. February 2021;143:115733.
2022	Andreev D, Kachler K, Kachler K, Schett G. Rheumatoid arthritis and osteoimmunology: the adverse impact of a deregulated immune system on bone metabolism. Bone. September 2022;162:116468.
2023	Cao G, Zhang S, Wang Y, Quan S, Yue C, Yao J, Alexander PG, Tan H. Pathogenesis of acquired heterotopic ossification: risk factors, cellular mechanisms, and therapeutic implications. Bone. March 2023;168:116655.
2020	Gregson CL, Bergen DJM, Leo P, Sessions RB, Wheeler L, Hartley A, Youlten S, Croucher PI, McInerney‐Leo AM, Fraser W, Tang JCY, Anderson L, Marshall M, Sergot L, Paternoster L, Smith GD, Brown MA, Hammond C, Kemp JP, Tobias JH, Duncan EL; The AOGC Consortium. A rare mutation in SMAD9 associated with high bone mass identifies the SMAD‐dependent BMP signaling pathway as a potential anabolic target for osteoporosis. J Bone Miner Res. January 2020;35(1):92-105.
2020	Xu J, Liu J, Gan Y, Dai K, Zhao J, Huang M, Huang Y, Zhuang Y, Zhang X. High‐dose TGF‐Β1 impairs mesenchymal stem cell–mediated bone regeneration via Bmp2 inhibition. J Bone Miner Res. January 2020;35(1):167-180.
2020	Sen B, Paradise CR, Xie Z, Sankaran J, Uzer G, Styner M, Meyer M, Dudakovic A, van Wijnen AJ, Rubin J. Β‐catenin preserves the stem state of murine bone marrow stromal cells through activation of EZH2. J Bone Miner Res. June 2020;35(6):1149-1162.
2020	Chen J, Hendriks M, Chatzis A, Ramasamy SK, Kusumbe AP. Bone vasculature and bone marrow vascular niches in health and disease. J Bone Miner Res. November 2020;35(11):2103-2120.
2022	Julien A, Perrin S, Martínez-Sarrà E, Kanagalingam A, Carvalho C, Luka M, Ménager M, Colnot C. Skeletal stem/progenitor cells in periosteum and skeletal muscle share a common molecular response to bone injury. J Bone Miner Res. August 2022;37(8):1545-1561.
2023	Yu T, Li G, Wang C, Li N, Yao R, Wang J. Defective joint development and maintenance in GDF6-related multiple synostoses syndrome. J Bone Miner Res. April 2023;38(4):568-577.
2017	Kelly NH. Transcriptomic Analysis of Cortical Versus Cancellous Bone in Response to Mechanical Loading and Estrogen Signaling [PhD thesis]. Ithaca, NY: Cornell University; January 2017.
2021	Rivera KO. Localized Neurotrophin Delivery Via Microparticles for Enhanced Bone Fracture Repair [PhD thesis]. San Francisco, University of California; 2021.