ArticleScientific reports2016
TGF-β regulates phosphorylation and stabilization of Sox9 protein in chondrocytes through p38 and Smad dependent mechanisms.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 113 citations in OpenAlex.
- PTEN-AKT2 regulates mixed lineage liver cancer development and sensitizes cancer cells to TGFβ treatment.Oncogene · 2026Article
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Intrinsic mechanisms and microenvironmental cues fine-tune plasticity of esophageal progenitors.Nature communications · 2026Article
- Article
- PTEN-AKT2 Regulates Mixed Lineage Liver Cancer Development and Sensitizes Cancer Cells to TGFβ Treatment.Research square · 2026Article
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Microgravity-induced transcriptional reprogramming in embryonic chicken limb bud-derived chondrogenic cultures.Frontiers in cell and developmental biology · 2026Article
- TGF-β signaling in heterotopic ossification: the pathogenesis and the target for its treatment.Journal of orthopaedic surgery and research · 2025Review
- Skeletal Maturity and Age-Related Changes in Immune Cells and Circulatory Factors Impair Large-Scale Bone Regeneration.Aging cell · 2025Article
- A comprehensive review of curcumin-based scaffolds in cartilage tissue engineering.Stem cell research & therapy · 2025Review
- Enhanced disc regeneration through CRISPR/Cas9-mediated SOX9 and TGFβ1 coexpression in tonsil-derived mesenchymal stromal cells.Stem cell research & therapy · 2025Article
- Sox9 regulates Papss2 mRNA expression through derepression of the transcriptional repressor, C/EBPβ, in chondrogenic cells.Gene reports · 2025Article
- Article
- Orthobiologics Revisited: A Concise Perspective on Regenerative Orthopedics.Current issues in molecular biology · 2025Review
- SOX9 haploinsufficiency reveals SOX9-Noggin interaction in BMP-SMAD signaling pathway in chondrogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis.eLife · 2024Article
- Distinct roles of SOX9 in self-renewal of progenitors and mesenchymal transition of the endothelium.Angiogenesis · 2024Article
- Role of integrin β1 and tenascin C mediate TGF-SMAD2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel.Regenerative biomaterials · 2024Article
- Scaffolds containing GAG-mimetic cellulose sulfate promote TGF-β interaction and MSC Chondrogenesis over native GAGs.Journal of biomedical materials research. Part A · 2023Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Members of the TGF-β superfamily are important regulators of chondrocyte function. Sox9, a key transcriptional regulator of chondrogenesis, is required for TGF-β-mediated regulation of specific cartilage genes. TGF-β can signal through a canonical, Smad-mediated pathway or non-conical pathways, including p38. Here we show that both pathways are activated in chondrocytes after treatment with TGF-β and that TGF-β stabilizes Sox9 protein and increases phosphorylation of Sox9. Mutagenesis of potential serine phosphorylation sites on Sox9 was used to demonstrate that serine 211 is required to maintain normal basal levels of Sox9 as well as mediate increased Sox9 levels in response to TGF-β. The serine 211 site is in a motif that is targeted by p38 kinase. We used siRNA and pharmacological agents to show that p38 and Smad3 independently regulate the phosphorylation and stability of Sox9. Previously, we demonstrated that Papss2 is a downstream transcriptional target of Sox9 and TGF-β. Here we show that p38 is required for TGF-β-mediated regulation of Papss2 mRNA. Together the results suggest a new mechanism for TGF-β-mediated gene regulation in chondrocytes via p38 and phosphorylation and stabilization of Sox9. Understanding how TGF-β regulates Sox9 may lead to identification of therapeutic targets for OA.
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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.