BMP antagonists in tissue development and disease

Annkatrin Correns; Laura-Marie A Zimmermann; Clair Baldock; Gerhard Sengle

doi:10.1016/j.mbplus.2021.100071

BMP antagonists in tissue development and disease

Matrix Biol Plus. 2021 Jun 11:11:100071. doi: 10.1016/j.mbplus.2021.100071. eCollection 2021 Aug.

Authors

Annkatrin Correns^{1

2}, Laura-Marie A Zimmermann^{1

2}, Clair Baldock^{3

4}, Gerhard Sengle^{1

2

5

6}

Affiliations

¹ Department of Paediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
² Center for Biochemistry, Faculty of Medicine, University Hospital of Cologne, Joseph-Stelzmann-Str. 52, 50931 Cologne, Germany.
³ Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, B.3016 Michael Smith Building, Oxford Road, M13 9PT, Manchester, United Kingdom.
⁴ Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Michael Smith Building, M13 9PT, Manchester, UK.
⁵ Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Str. 21, 50931 Cologne, Germany.
⁶ Cologne Centre for Musculoskeletal Biomechanics (CCMB), Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.

Abstract

Bone morphogenic proteins (BMPs) are important growth regulators in embryogenesis and postnatal homeostasis. Their tight regulation is crucial for successful embryonic development as well as tissue homeostasis in the adult organism. BMP inhibition by natural extracellular biologic antagonists represents the most intensively studied mechanistic concept of BMP growth factor regulation. It was shown to be critical for numerous developmental programs, including germ layer specification and spatiotemporal gradients required for the establishment of the dorsal-ventral axis and organ formation. The importance of BMP antagonists for extracellular matrix homeostasis is illustrated by the numerous human connective tissue disorders caused by their mutational inactivation. Here, we will focus on the known functional interactions targeting BMP antagonists to the ECM and discuss how these interactions influence BMP antagonist activity. Moreover, we will provide an overview about the current concepts and investigated molecular mechanisms modulating BMP inhibitor function in the context of development and disease.

Keywords: ALK3, anaplastic lymphoma kinase 3; ATF2, activating transcription factor 2; ActR, activin receptor; BDB2, brachydactyly type B2; BISC, BMP-induced signalling complex; BMP antagonists; BMPER, BMP binding endothelial regulator; BMPs, bone morphogenetic proteins; Bone morphogenetic protein (BMP); CAN, cerberus and DAN; CDD, craniodiaphyseal dysplasia; CHRD domain, chordin specific domain; CUB domain, for complement C1r/C1s, Uegf, Bmp1 domain; Connective tissue disorder; Cv2, crossveinless-2; DAN, differential screening selected gene aberrative in neuroblastoma; DSD, diaphanospondylodysostosis; Dpp, decapentaplegic; ECM, extracellular matrix; ERK, extracellular signal-regulated kinases; Extracellular matrix (ECM); FMF, fibrillin microfibrils; HS, heparan sulphate; HSPGs, heparan sulphate proteoglycans; MAPKs, mitogen-activated protein kinases; MGC1, megalocornea 1; PI3K, phosphoinositide 3-kinase; PRDC, protein related to DAN and Cerberus; SOST, sclerostin; SYNS1, multiple synostoses syndrome 1; Scw, screw; Sog, short gastrulation; TCC, tarsal-carpal coalition syndrome; TGF-β, transforming growth factor- β; Tld, tolloid; Tsg, twisted gastrulation; VBCH, Van Buchem disease; Xlr/Tll, xolloid-related metalloprotease; vWC, von Willebrand factor type C; vWD, von Willebrand factor type D.

Publication types

Review