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Cited by 445TGF-β signaling in diseasesBone Metabolism and DiseasesOsteoarthritis Treatment and Mechanisms

The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease

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Wu, Mengrui, Wu, Shali, Chen, Wei, Li, Yi-Ping·2024·Cell Research
DOI 10.1038/s41422-023-00918-9PMC PMC10837209
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Abstract

Transforming growth factor-βs (TGF-βs) and bone morphometric proteins (BMPs) belong to the TGF-β superfamily and perform essential functions during osteoblast and chondrocyte lineage commitment and differentiation, skeletal development, and homeostasis. TGF-βs and BMPs transduce signals through SMAD-dependent and -independent pathways; specifically, they recruit different receptor heterotetramers and R-Smad complexes, resulting in unique biological readouts. BMPs promote osteogenesis, osteoclastogenesis, and chondrogenesis at all differentiation stages, while TGF-βs play different roles in a stage-dependent manner. BMPs and TGF-β have opposite functions in articular cartilage homeostasis. Moreover, TGF-β has a specific role in maintaining the osteocyte network. The precise activation of BMP and TGF-β signaling requires regulatory machinery at multiple levels, including latency control in the matrix, extracellular antagonists, ubiquitination and phosphorylation in the cytoplasm, nucleus-cytoplasm transportation, and transcriptional co-regulation in the nuclei. This review weaves the background information with the latest advances in the signaling facilitated by TGF-βs and BMPs, and the advanced understanding of their diverse physiological functions and regulations. This review also summarizes the human diseases and mouse models associated with disordered TGF-β and BMP signaling. A more precise understanding of the BMP and TGF-β signaling could facilitate the development of bona fide clinical applications in treating bone and cartilage disorders.

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  • SMAD1 has been reported to repress Lgr5+ stem cell signature genes, thereby limiting stem cell expansion and maintaining intestinal homeostasis.

    “As a major receptor-activated SMADs (R-SMADs) downstream of BMP pathway, SMAD1 has been reported to repress Lgr5+ stem cell signature genes, thereby limiting stem cell expansion and maintaining intestinal homeostasis.50–52”

    From Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer (2026) · cites this paper as [50]

    The 'Canonical and non-canonical signaling' section identifies SMAD1 as a receptor-regulated SMAD activated by BMP signaling. Our copy does not report that SMAD1 represses Lgr5+ stem cell signature genes or limits intestinal stem cell expansion; searches for Lgr5 and intestinal stem cell expansion found no supporting passage. Page numbers were not available in the indexed copy. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Wu, M., Wu, S., Chen, W., & Li, Y.-P.
Affiliations
  • Zhejiang University (CN)
  • Tulane University (US)
Corresponding author
Wu, Mengrui
ORCID
Venue
Cell Research
Publisher
Springer Science and Business Media LLC
Published
2024-01-24
Volume
34
Issue
2
Pages
101-123
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
DOI
10.1038/s41422-023-00918-9
PMC
PMC10837209
OpenAlex
W4391168196
Cited by
445
References
5
Citations by year
2026: 174 · 2025: 207 · 2024: 64
FWCI
18.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR075735, AR070135)
  • U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (DE023813, DE028264)
  • National Natural Science Foundation of China (81900806, 32070814)
  • U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG056438)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
Keywords
TGF-beta signaling, BMP signaling, TGF-beta superfamily, skeletal development, chondrogenesis, osteogenic differentiation, chondrogenic differentiation, osteoclastogenesis, articular cartilage homeostasis, osteocyte network, Smad signaling, BMP antagonists, ubiquitination, transcriptional co-regulation, bone disease
MeSH terms
Animals, Bone and Bones, Cartilage, Homeostasis, Humans, Transforming Growth Factor beta, Bone Morphogenetic Proteins, Chondrogenesis, Mice

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