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Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton

Canalis, Ernesto, Economides, Aris N., Gazzerro, Elisabetta·2003·Endocrine Reviews

Abstract

Skeletal homeostasis is determined by systemic hormones and local factors. Bone morphogenetic proteins (BMP) are unique because they induce the differentiation of mesenchymal cells toward cells of the osteoblastic lineage and also enhance the differentiated function of the osteoblast. However, the activity of BMPs needs to be tempered by intracellular and extracellular antagonists. BMPs bind to specific receptors and signal by phosphorylating the cytoplasmic proteins mothers against decapentaplegic (Smad) 1 and 5, which form heterodimers with Smad 4, and after nuclear translocation regulate transcription. BMP antagonists can be categorized as pseudoreceptors that compete with signaling receptors, inhibitory Smads that block signaling, intracellular binding proteins that bind Smad 1 and 5, and factors that induce ubiquitination and proteolysis of signaling Smads. In addition, a large number of extracellular proteins that bind BMPs and prevent their binding to signaling receptors have emerged. They are the components of the Spemann organizer, noggin, chordin, and follistatin, members of the Dan/Cerberus family, and twisted gastrulation. The antagonists tend to be specific for BMPs and are regulated by BMPs, indicating the existence and need of local feedback mechanisms to temper BMP cellular activities.

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Metadata

Authors
Canalis, E., Economides, A. N., & Gazzerro, E.
Venue
Endocrine Reviews
Published
2003-04-01
Volume
24
Issue
2
Pages
218-235
ISSN
  • 0163-769X (ISSN-L)
  • 1945-7189
OpenAlex
W2110149781
Cited by
863
References
10
FWCI
16.94
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton. https://app.cochat.ai/papers/10.1210/er.2002-0023
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Canalis, E., Economides, A. N., & Gazzerro, E. (2003). Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton. Endocrine Reviews. https://doi.org/10.1210/er.2002-0023

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