ArticleJournal of cellular biochemistry2012
Ski inhibits TGF-β/phospho-Smad3 signaling and accelerates hypertrophic differentiation in chondrocytes.
Article in Journal of cellular biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- A new mutational hotspot in the SKI gene in the context of MFS/TAA molecular diagnosis.Human genetics · 2020Trial
- Single-cell RNA sequencing of healthy and diseased rat temporomandibular joint condyle cartilage.PloS one · 2026Article
- Potential roles of histone deacetylases in diabetic wound healing.World journal of diabetes · 2025Review
- miR-204-5p Mitigates Disc Degeneration via SKI-Mediated Modulation of Apoptotic Signaling and Matrix Remodeling in Nucleus Pulposus.The American journal of pathology · 2025Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Article
- Integrative Analysis Reveals the Diverse Effects of 3D Stiffness upon Stem Cell Fate.International journal of molecular sciences · 2023Article
- Primary Cilia Direct Murine Articular Cartilage Tidemark Patterning Through Hedgehog Signaling and Ambulatory Load.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Article
- SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration.Apoptosis : an international journal on programmed cell death · 2022Article
- COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis.International journal of molecular sciences · 2021Article
- Strategies to Modulate the Redifferentiation of Chondrocytes.Frontiers in bioengineering and biotechnology · 2021Review
- Concise Review: The Regulatory Mechanism of Lysine Acetylation in Mesenchymal Stem Cell Differentiation.Stem cells international · 2020Review
- Review
- Mir-29b promotes human aortic valve interstitial cell calcification via inhibiting TGF-β3 through activation of wnt3/β-catenin/Smad3 signaling.Journal of cellular biochemistry · 2018Article
- The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation.Experimental and therapeutic medicine · 2018Article
- TGF-β Stimulates Endochondral Differentiation after Denervation.International journal of medical sciences · 2017Article
- Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate.PLoS genetics · 2016Article
- MiR-206 Attenuates Denervation-Induced Skeletal Muscle Atrophy in Rats Through Regulation of Satellite Cell Differentiation via TGF-β1, Smad3, and HDAC4 Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection.The Journal of experimental medicine · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Since transforming growing factor-β (TGF-β)/Smad signaling inhibits chondrocyte maturation, endogenous negative regulators of TGF-β signaling are likely also important regulators of the chondrocyte differentiation process. One such negative regulator, Ski, is an oncoprotein that is known to inhibit TGF-β/Smad3 signaling via its interaction with phospho-Smad3 and recruitment of histone deacetylases (HDACs) to the DNA binding complex. Based on this, we hypothesized that Ski inhibits TGF-β signaling and accelerates maturation in chondrocytes via recruitment of HDACs to transcriptional complexes containing Smads. We tested this hypothesis in chick upper sternal chondrocytes (USCs), where gain and loss of Ski expression experiments were performed. Over-expression of Ski not only reversed the inhibitory effect of TGF-β on the expression of hypertrophic marker genes such as type X collagen (colX) and osteocalcin, it induced these genes basally as well. Conversely, knockdown of Ski by RNA interference led to a reduction of colX and osteocalcin expression under basal conditions. Furthermore, Ski blocked TGF-β induction of cyclinD1 and caused a basal up-regulation of Runx2, consistent with the observed acceleration of hypertrophy. Regarding mechanism, not only does Ski associate with phospho-Smad2 and 3, but its association with phospho-Smad3 is required for recruitment of HDAC4 and 5. Implicating this recruitment of HDACs in the phenotypic effects of Ski in chondrocytes, the HDAC inhibitor SAHA reversed the up-regulation of colX and osteocalcin in Ski over-expressing cells. These results suggest that inhibition of TGF-β signaling by Ski, which involves its association with phospho-Smad3 and recruitment of HDAC4 and 5, leads to accelerated chondrocyte differentiation.
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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.