ArticleOsteoarthritis and cartilage2017
SOX9 protein is stabilized by TGF-β and regulates PAPSS2 mRNA expression in chondrocytes.
Article in Osteoarthritis and cartilage, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
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- miR-145-5p combined with miR-140-5p regulates the differentiation of bone marrow mesenchymal stem cells into nucleus pulposus cells and its mechanism in the treatment of intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2026Article
- 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) is a potential diagnostic and prognostic biomarker in colon adenocarcinoma.Scientific reports · 2026Article
- Platelet-rich plasma in cartilage repair: biological mechanisms and clinical perspectives.Frontiers in sports and active living · 2026Review
- MicroRNA-mediated mechanotransduction and chondrocyte differentiation in mesenchymal stem cells.Animal cells and systems · 2026Review
- From Therapeutic Dilemma to Precision Modulation: Harnessing Biomaterials to Target the Dual Face of TGF-β in Osteoarthritis.Journal of inflammation research · 2026Review
- Sox9 regulates Papss2 mRNA expression through derepression of the transcriptional repressor, C/EBPβ, in chondrogenic cells.Gene reports · 2025Article
- The Role of Exerkines in the Treatment of Knee Osteoarthritis: From Mechanisms to Exercise Strategies.Orthopaedic surgery · 2025Review
- Review
- Sericin promotes chondrogenic proliferation and differentiation via glycolysis and Smad2/3 TGF-β signaling inductions and alleviates inflammation in three-dimensional models.Scientific reports · 2024Article
- The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis.International journal of molecular sciences · 2023Article
- Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis.APL bioengineering · 2023Article
- Three-dimensional hydrogel with human Wharton jelly-derived mesenchymal stem cells towards nucleus pulposus niche.Frontiers in bioengineering and biotechnology · 2023Article
- Mast4 determines the cell fate of MSCs for bone and cartilage development.Nature communications · 2022Article
- Transcriptomic Profiling of Gene Expression Associated with Granulosa Cell Tumor Development in a Mouse Model.Cancers · 2022Article
- Regulatory Mechanisms ofInternational journal of molecular sciences · 2022Review
- Dysregulated overexpression of Sox9 induces fibroblast activation in pulmonary fibrosis.JCI insight · 2021Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe previously identified 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) as a transcriptional target of transforming growth factor β (TGF-β) in chondrocytes. PAPSS2 is required for proper sulfation of proteoglycans in cartilage. Defective sulfation in the matrix results in alterations in mechanical properties of the cartilage that would be expected to result in degeneration. The objective of this study was to identify factors that regulate PAPSS2 expression and compare to a known TGF-β responsive gene, proteoglycan 4/lubricin (PRG4). In this study, TGF-β-mediated regulation of SOX9 was characterized, and the involvement of SOX9 in regulation of PAPSS2 mRNA was investigated.
designPrimary bovine articular chondrocytes grown in micromass culture and ATDC5 cells were used as the model system. Adenoviruses were used to express SOX9 and SMAD3. siRNA was used to knock-down Sox9 and Smad3. Western blot and real-time quantitative RT-PCR (qPCR) were used to measure changes in protein and mRNA levels in response to treatment.
resultsOver-expression of SOX9 was sufficient to up-regulate PAPSS2 mRNA. TGF-β treatment of SOX9-expressing cells resulted in enhanced up-regulation of PAPSS2 mRNA, suggesting that SOX9 cooperates with TGF-β signaling. Furthermore, Sox9 was required for full TGF-β-mediated induction of Papss2. In contrast, PRG4 was regulated by SMAD3 but not SOX9. SOX9 protein levels were increased after treatment with TGF-β, although SOX9 mRNA was not. SOX9 protein was post-translationally stabilized after treatment with TGF-β.
conclusionsTGF-β stabilizes SOX9 protein, and SOX9 is sufficient and necessary for TGF-β-mediated regulation of PAPSS2 mRNA, providing a novel mechanism for TGF-β-mediated gene regulation in chondrocytes.
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