ArticleMolecular and cellular biology1997
SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(II) collagen gene.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 393 papers, 1 of them a synthesis that pooled it.
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Who cites it
393 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,069 citations in OpenAlex.
- Reserve or Resident Progenitors in Cartilage? Comparative Analysis of Chondrocytes versus Chondroprogenitors and Their Role in Cartilage Repair.Cartilage · 2018Pooled it
- Effects of CD14 macrophages and proinflammatory cytokines on chondrogenesis in osteoarthritic synovium-derived stem cells.Tissue engineering. Part A · 2014Trial
- Epigenetic regulation of vertebrate limb development: from field specification to tissue morphogenesis.Epigenetics · 2026Review
- Nascent Extracellular Matrix Converts Biomaterial Cues into Cell Fate Decisions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An Efficient Spheroid Manufacturing Workflow for WJ-MSCs: Comparative Evaluation of Immediate 3D Aggregation and Conventional 2D Stabilization.Bioengineering (Basel, Switzerland) · 2026Article
- Compressive stress-driven mechanosignaling in chondrocytes: From molecular mechanism to scaffold engineering and translational opportunities.Materials today. Bio · 2026Review
- Bioorthogonal Tuning of Hydrogel Stiffness Promotes Zonal Redifferentiation of Passaged Chondrocytes.bioRxiv : the preprint server for biology · 2026Article
- Stage- and cluster-specific regulation of chondrogenic gene programs by Sox9 in mouse embryonic limb buds.iScience · 2026Article
- High glucose upregulates BMAL1 in chondrocytes from macroscopically normal and osteoarthritic human cartilage but this only results in increased collagen synthesis in chondrocytes from macroscopically normal cartilage regions.Osteoarthritis and cartilage open · 2026Article
- MicroRNA-mediated mechanotransduction and chondrocyte differentiation in mesenchymal stem cells.Animal cells and systems · 2026Review
- A Vascularized Microphysiological System Reproducing Endochondral Ossification in Vitro to Study Ewing Sarcoma Proliferation and Migration.Advanced functional materials · 2026Article
- Thymoquinone inhibited the chondrogenic differentiation of tendon-derived stem cells caused by tendon injury.World journal of stem cells · 2025Article
- Sox9 regulates Papss2 mRNA expression through derepression of the transcriptional repressor, C/EBPβ, in chondrogenic cells.Gene reports · 2025Article
- Transcriptomic Profiling of Zebrafish Mutant forInternational journal of molecular sciences · 2025Article
- Functional characterization of SOX5 variant causing Lamb-Shaffer syndrome and literature review of variants in the SOX5 gene.Orphanet journal of rare diseases · 2025Review
- Creb5 controls its own expression and directly induces the joint interzone regulatory program.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NSAID-mediated cyclooxygenase inhibition disrupts ectodermal derivative formation in axolotl embryos.bioRxiv : the preprint server for biology · 2025Article
- The Expression Level of SOX Family Transcription Factors' mRNA as a Diagnostic Marker for Osteoarthritis.Journal of clinical medicine · 2025Article
- MLL4 regulates postnatal palate growth and midpalatal suture development.Frontiers in cell and developmental biology · 2025Article
- MLL4 regulates postnatal palate growth and midpalatal suture development.bioRxiv : the preprint server for biology · 2024Article
333 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
The identification of mutations in the SRY-related SOX9 gene in patients with campomelic dysplasia, a severe skeletal malformation syndrome, and the abundant expression of Sox9 in mouse chondroprogenitor cells and fully differentiated chondrocytes during embryonic development have suggested the hypothesis that SOX9 might play a role in chondrogenesis. Our previous experiments with the gene (Col2a1) for collagen II, an early and abundant marker of chondrocyte differentiation, identified a minimal DNA element in intron 1 which directs chondrocyte-specific expression in transgenic mice. This element is also a strong chondrocyte-specific enhancer in transient transfection experiments. We show here that Col2a1 expression is closely correlated with high levels of SOX9 RNA and protein in chondrocytes. Our experiments indicate that the minimal Col2a1 enhancer is a direct target for Sox9. Indeed, SOX9 binds to a sequence of the minimal Col2a1 enhancer that is essential for activity in chondrocytes, and SOX9 acts as a potent activator of this enhancer in cotransfection experiments in nonchondrocytic cells. Mutations in the enhancer that prevent binding of SOX9 abolish enhancer activity in chondrocytes and suppress enhancer activation by SOX9 in nonchondrocytic cells. Other SOX family members are ineffective. Expression of a truncated SOX9 protein lacking the transactivation domain but retaining DNA-binding activity interferes with enhancer activation by full-length SOX9 in fibroblasts and inhibits enhancer activity in chondrocytes. Our results strongly suggest a model whereby SOX9 is involved in the control of the cell-specific activation of COL2A1 in chondrocytes, an essential component of the differentiation program of these cells. We speculate that in campomelic dysplasia a decrease in SOX9 activity would inhibit production of collagen II, and eventually other cartilage matrix proteins, leading to major skeletal anomalies.
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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.