ArticleThe Journal of biological chemistry2017
A Novel Regulatory Mechanism of Type II Collagen Expression via a SOX9-dependent Enhancer in Intron 6.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Ex Vivo Preconditioning as a Useful Tool for Modification of the Extracellular Matrix of Multipotent Mesenchymal Stromal Cells.International journal of molecular sciences · 2025Review
- Mechanism of Intervertebral Disc Degeneration via the β-Catenin/CCL2 Pathway in Sox9 Conditional Knockout Mice.JOR spine · 2025Article
- SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma.Molecular neurobiology · 2024Article
- Collagen-Derived Dipeptide Pro-Hyp Enhanced ATDC5 Chondrocyte Differentiation under Hypoxic Conditions.Molecules (Basel, Switzerland) · 2023Article
- Network model integrated with multi-omic data predicts MBNL1 signals that drive myofibroblast activation.iScience · 2023Article
- Multiparity and Aging Impact Chondrogenic and Osteogenic Potential at Symphyseal Enthesis: New Insights into Interpubic Joint Remodeling.International journal of molecular sciences · 2023Article
- Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells.Scientific reports · 2022Article
- Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development.Nature communications · 2022Article
- Histone H3K27 demethylase UTX compromises articular chondrocyte anabolism and aggravates osteoarthritic degeneration.Cell death & disease · 2022Article
- Article
- Integrated regulation of chondrogenic differentiation in mesenchymal stem cells and differentiation of cancer cells.Cancer cell international · 2022Review
- Parathyroid hormone promotes cartilage healing after free reduction of mandibular condylar fractures by upregulating Sox9.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes.Journal of orthopaedic surgery and research · 2021Article
- Human Umbilical Mesenchymal Stromal Cells Mixed with Hyaluronan Transplantation Decreased Cartilage Destruction in a Rabbit Osteoarthritis Model.Stem cells international · 2021Article
- Histone ChIP-Seq identifies differential enhancer usage during chondrogenesis as critical for defining cell-type specificity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Targeted and sustained Sox9 expression in mouse hypertrophic chondrocytes causes severe and spontaneous osteoarthritis by perturbing cartilage homeostasis.American journal of translational research · 2020Article
- TheJournal of clinical medicine · 2019Article
- Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture.Stem cells translational medicine · 2019Article
- How does the promoter of an oocyte-specific gene function in male germ cells?The Journal of reproduction and development · 2018Article
- Fox proteins are modular competency factors for facial cartilage and tooth specification.Development (Cambridge, England) · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type II collagen α1 is specific for cartilaginous tissues, and mutations in its gene are associated with skeletal diseases. Its expression has been shown to be dependent on SOX9, a master transcription factor required for chondrogenesis that binds to an enhancer region in intron 1. However, ChIP sequencing revealed that SOX9 does not strongly bind to intron 1, but rather it binds to intron 6 and a site 30 kb upstream of the transcription start site. Here, we aimed to determine the role of the novel SOX9-binding site in intron 6. We prepared reporter constructs that contain a Col2a1 promoter, intron 1 with or without intron 6, and the luciferase gene. Although the reporter constructs were not activated by SOX9 alone, the construct that contained both introns 1 and 6 was activated 5-10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient-transfection assays in 293T cells. This enhancement was also observed in rat chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is necessary both for Col2a1 expression and SOX9 binding. Furthermore, SOX9, but not SOX5, binds to this region as demonstrated in an electrophoretic mobility shift assay, although both SOX9 and SOX5 bind to a larger 325-bp fragment of intron 6 containing this small sequence. These findings suggest a novel mechanism of action of SOX5/6; namely, the SOX9/5/6 combination enhances Col2a1 transcription through a novel enhancer in intron 6 together with the enhancer in intron 1.
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