ArticleThe Journal of cell biology2001
TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage.
Article in The Journal of cell biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 301 papers, 4 of them syntheses that pooled it.
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Who cites it
301 citing papers in PubMed, 4 syntheses or guidelines pooled it, 637 citations in OpenAlex.
- Pooled it
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- Synchronizing the Osteochondral Regeneration Process through Spatial Patterning of Stable and Hypertrophic Cartilage Organoids.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Role of external forces in the mechanobiology of stem and differentiated chondrogenic cells embedded in a tissue-engineered construct for cartilage repair.Journal of biomedical science · 2026Review
- LncRNA HOXC-AS3 prevents chondrocyte senescence and osteoarthritis progression through miR-615-3p sponging and RRBP1 interaction.Cell & bioscience · 2026Article
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- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Molecular Mechanisms of Chondrocyte Hypertrophy Mediated by Physical Cues and Therapeutic Strategies in Osteoarthritis.International journal of molecular sciences · 2026Review
- Role of Notch signaling pathway in joint homeostasis and osteoarthritis.Frontiers in bioengineering and biotechnology · 2026Review
- Chondrogenic Differentiation of Stem Cells for Cartilage Regeneration: Advances and Future Perspectives.Tissue engineering and regenerative medicine · 2026Review
- Intra-Articular Delivery of Nanoemulsified Curcumin Ameliorates Joint Degeneration in a Chemically Induced Model of Osteoarthritis.International journal of molecular sciences · 2025Article
- Insights from pharmacovigilance databases, clinical cohorts and preclinical models into VEGF(R) inhibitor-induced arthritis in cancer.Communications medicine · 2025Article
- Characterizing the Long Non-Coding RNA Profile of Endometrial Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Anti-Inflammatory Role in Osteoarthritis.International journal of molecular sciences · 2025Article
- Molecular Consequences ofInternational journal of molecular sciences · 2025Article
- Osteoarthritis as an evolutionary legacy: Biological ageing and chondrocyte hypertrophy.Osteoarthritis and cartilage open · 2025Review
241 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Endochondral ossification begins from the condensation and differentiation of mesenchymal cells into cartilage. The cartilage then goes through a program of cell proliferation, hypertrophic differentiation, calcification, apoptosis, and eventually is replaced by bone. Unlike most cartilage, articular cartilage is arrested before terminal hypertrophic differentiation. In this study, we showed that TGF-beta/Smad3 signals inhibit terminal hypertrophic differentiation of chondrocyte and are essential for maintaining articular cartilage. Mutant mice homozygous for a targeted disruption of Smad3 exon 8 (Smad3(ex8/ex8)) developed degenerative joint disease resembling human osteoarthritis, as characterized by progressive loss of articular cartilage, formation of large osteophytes, decreased production of proteoglycans, and abnormally increased number of type X collagen-expressing chondrocytes in synovial joints. Enhanced terminal differentiation of epiphyseal growth plate chondrocytes was also observed in mutant mice shortly after weaning. In an in vitro embryonic metatarsal rudiment culture system, we found that TGF-beta1 significantly inhibits chondrocyte differentiation of wild-type metatarsal rudiments. However, this inhibition is diminished in metatarsal bones isolated from Smad3(ex8/ex8) mice. These data suggest that TGF-beta/Smad3 signals are essential for repressing articular chondrocyte differentiation. Without these inhibition signals, chondrocytes break quiescent state and undergo abnormal terminal differentiation, ultimately leading to osteoarthritis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.