Affinage

COL2A1

Collagen alpha-1(II) chain · UniProt P02458

Length
1487 aa
Mass
141.8 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL2A1 encodes the alpha-1 chain of type II procollagen, the principal structural collagen of cartilage, and is essential for skeletal development and extracellular matrix integrity (PMID:3857598, PMID:11725236). Transcription is driven by SOX9 binding a 48-bp intron 1 enhancer containing HMG-like sites, with PKA phosphorylation of SOX9 at Ser64/Ser211 augmenting this activation, while IFN-γ (via JAK1/JAK2/Stat1α), ESE-1, ELF3, and high-dose SOX9 itself repress COL2A1 through its proximal promoter (PMID:9614106, PMID:10805756, PMID:12223098, PMID:18044710, PMID:27310669, PMID:12713737). The pre-mRNA undergoes developmentally regulated alternative splicing of exon 2 (IIA-to-IIB switch during chondrocyte maturation), controlled by splice-site sequences that serve as the molecular switch for isoform selection (PMID:18023161, PMID:22248926). Pathogenic glycine substitutions in the triple-helical domain cause procollagen misfolding, intracellular retention, and impaired fibril assembly (procollagen suicide), while haploinsufficiency from premature stop codons produces milder skeletal phenotypes including Stickler syndrome (PMID:1374906, PMID:1881905, PMID:12359167, PMID:11725236).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1985 High

    Identification of COL2A1 as the human type II collagen gene on chromosome 12 with tissue-restricted expression established the foundational molecular identity of the major cartilage collagen.

    Evidence Southern blotting, DNA sequencing, mRNA hybridization, and somatic cell hybrid mapping

    PMID:3857598 PMID:6594770

    Open questions at the time
    • Full exon-intron structure not yet resolved
    • No regulatory elements mapped
    • Protein biochemistry of the gene product not yet characterized from this locus
  2. 1991 High

    A transgenic minigene model demonstrated that truncated COL2A1 chains poison normal procollagen trimers through disulfide-linked co-assembly and co-degradation ('procollagen suicide'), revealing how dominant-negative mutations cause chondrodysplasia.

    Evidence Transgenic mice expressing partially deleted COL2A1 minigene with biochemical analysis of chondrocyte procollagen chains

    PMID:1881905

    Open questions at the time
    • Quantitative threshold of mutant chain incorporation needed to trigger degradation unknown
    • Contribution of ER quality control pathways not addressed
  3. 1992 High

    Direct biochemical analysis of a Gly574Ser substitution showed that triple-helical glycine mutations impair procollagen processing, block intracellular transport, and disrupt fibril assembly, defining the molecular pathology of severe type II collagenopathies.

    Evidence Cultured patient chondrocytes analyzed by electrophoretic collagen analysis, SSCP, and direct sequencing

    PMID:1374906

    Open questions at the time
    • Structural basis for differential severity of different glycine substitutions not resolved
    • Downstream cellular stress responses not characterized
  4. 1995 Medium

    Reporter studies revealed that COL2A1 intron 1 sequences drive higher transcriptional activity in early chondrogenesis than in mature chondrocytes, indicating stage-specific regulatory mechanisms before the responsible transcription factor was identified.

    Evidence Transient transfection of promoter/intron reporter constructs in micromass and sternal chondrocytes, with transgenic mouse confirmation

    PMID:8785590

    Open questions at the time
    • Identity of the stage-specific transcription factor not yet known
    • Minimal enhancer element not defined
  5. 1998 High

    Identification of a 48-bp intron 1 enhancer with three HMG-like sites, all required for chondrocyte-specific expression, and demonstration that SOX9 directly binds this enhancer to activate COL2A1 transcription, established the core transcriptional mechanism for cartilage-specific collagen gene regulation.

    Evidence Transgenic mouse reporters, site-directed mutagenesis, EMSA, transient transfection, and parallel characterization with Col11a2 enhancer

    PMID:9614106 PMID:9614107

    Open questions at the time
    • Identity of cofactors binding sites 1 and 2 unresolved
    • Chromatin context of enhancer activity not addressed
  6. 2000 High

    Discovery that PKA directly phosphorylates SOX9 at Ser64 and Ser211 to enhance its DNA-binding and transactivation of the Col2a1 enhancer revealed a signaling axis linking cAMP/PKA to cartilage gene expression.

    Evidence Yeast two-hybrid, in vitro kinase assay, phosphospecific antibody, SOX9 phosphomutant cotransfection, immunohistochemistry

    PMID:10805756

    Open questions at the time
    • Upstream signals activating PKA in chondrocytes not defined
    • Whether phosphorylation alters SOX9 cofactor recruitment unknown
  7. 2001 Medium

    Heterozygous Col2a1 knockout mice showed shorter limb bones and premature vertebral ossification, establishing that haploinsufficiency alone is sufficient to produce skeletal abnormalities and modeling human Stickler syndrome-like phenotypes.

    Evidence Heterozygous knockout mice analyzed by radiography, histology, immunohistochemistry, and in situ hybridization

    PMID:11725236

    Open questions at the time
    • Compensation mechanisms at 15 months not molecularly characterized
    • Not directly linked to specific human Stickler mutations
  8. 2002 Medium

    A transgenic Arg519Cys model showed dilated Golgi cisternae and reduced fibril density in articular cartilage, confirming intracellular retention as a general mechanism for glycine substitution pathology beyond the Gly574Ser mutation.

    Evidence Transgenic mice expressing human COL2A1 R519C, electron microscopy, histology

    PMID:12359167

    Open questions at the time
    • ER stress and unfolded protein response not directly measured
    • Whether different glycine substitutions trigger distinct retention mechanisms unclear
  9. 2003 High

    Two repressive pathways were identified: IFN-γ represses COL2A1 through the core promoter via JAK1/JAK2/Stat1α without a direct GAS element, and high SOX9 doses paradoxically repress COL2A1 through the proximal promoter, adding inhibitory layers to the transcriptional circuit.

    Evidence JAK-deficient cell lines with rescue, dominant-negative Stat1α, promoter deletion reporters; graded SOX9 overexpression in primary and passaged chondrocytes

    PMID:12223098 PMID:12713737

    Open questions at the time
    • Mechanism by which Stat1α interacts with general transcription machinery at COL2A1 unknown
    • Physiological context where high SOX9 repression operates in vivo not established
  10. 2007 Medium

    Characterization of four COL2A1 splice isoforms (IIA, IIB, IIC, IID) and demonstration that an alternative 5' splice site in exon 2 regulates isoform abundance revealed unexpected complexity in post-transcriptional regulation of type II collagen.

    Evidence RT-PCR, Southern analysis, and COL2A1 mini-gene splicing assays in cell lines

    PMID:18023161

    Open questions at the time
    • Trans-acting splicing factors controlling exon 2 inclusion not identified
    • Functional significance of IIC and IID isoforms unknown
  11. 2008 High

    IL-1β-induced ESE-1 was shown to directly bind tandem ETS sites in the COL2A1 promoter and repress transcription, while ETS-1 antagonizes this effect, linking inflammatory NF-κB signaling to sustained COL2A1 suppression in arthritic cartilage.

    Evidence ChIP, EMSA, siRNA knockdown of ESE-1/ETS-1, promoter deletion analysis in chondrocytes

    PMID:18044710

    Open questions at the time
    • Whether ESE-1 repression operates in human osteoarthritis cartilage in vivo not confirmed
    • Interplay between ESE-1 and SOX9 pathways not resolved
  12. 2012 High

    A knock-in mouse constitutively expressing the IIA isoform proved that the exon 2 splice-site sequence itself is the molecular switch for the IIA-to-IIB transition, and that this switch is dispensable for gross skeletal development, while Nkx3.2 was shown to directly bind the Col2a1 enhancer and activate transcription independently of Sox9.

    Evidence Knock-in mouse model with developmental RT-PCR and mini-gene validation; ChIP and siRNA in mesenchymal cells for Nkx3.2

    PMID:22248926 PMID:22511961

    Open questions at the time
    • Subtle cartilage quality defects in IIA-only mice not fully assessed
    • Whether Nkx3.2 and Sox9 bind simultaneously or compete at the enhancer unknown
  13. 2014 Medium

    Discovery that Set7/9 and SirT1 co-occupy the COL2A1 promoter and that Set7/9 restrains SirT1 deacetylase activity to maintain activating histone marks linked epigenetic chromatin remodeling to COL2A1 regulation during chondrocyte dedifferentiation.

    Evidence ChIP-reChIP, 3D alginate bead chondrocyte culture, histone modification immunochemistry

    PMID:23873758

    Open questions at the time
    • Causal evidence (Set7/9 loss-of-function effect on endogenous COL2A1) not provided
    • Whether this mechanism operates in vivo during cartilage homeostasis unknown
  14. 2016 Medium

    ELF3 was identified as a repressor that directly binds the SOX9 HMG domain and inhibits SOX9/CBP-p300 histone acetyltransferase activity at the Col2a1 enhancer, defining a protein-protein mechanism of COL2A1 repression distinct from promoter-binding repressors.

    Evidence Co-transfection with truncated Sox9 fragments, Gal4-Sox9 reporter, HAT activity assay, domain mapping

    PMID:27310669

    Open questions at the time
    • ELF3-SOX9 interaction not confirmed by co-immunoprecipitation of endogenous proteins
    • In vivo relevance in cartilage not demonstrated
  15. 2021 Medium

    Identification of CDC5L as a splicing factor that directly binds Col2a1 pre-mRNA and is required for its efficient splicing added a post-transcriptional regulatory node upstream of mature mRNA production.

    Evidence RNA-binding protein immunoprecipitation, siRNA/shRNA knockdown, RT-PCR splicing efficiency, metatarsal organ culture

    PMID:34298017

    Open questions at the time
    • Whether CDC5L specifically controls the IIA/IIB exon 2 switch or general splicing efficiency unclear
    • No direct demonstration that CDC5L splicing defect drives cartilage pathology in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identities of cofactors binding HMG-like sites 1 and 2 of the 48-bp enhancer, the full spectrum of trans-acting splicing regulators controlling exon 2 inclusion, and the structural basis for genotype-phenotype severity differences among glycine substitutions remain unresolved.
  • Sites 1/2 binding proteins never identified
  • No structural model of mutant procollagen trimer explaining severity gradients
  • Functional roles of IIC and IID isoforms completely unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0031012 extracellular matrix 4 GO:0005576 extracellular region 3
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1266738 Developmental Biology 3
Partners
CDC5LELF3ESE1NKX3-2SETD7SIRT1SOX9SP1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 COL2A1 was identified as the human type II collagen gene, localized to chromosome 12, encoding a ~30 kb gene with expression restricted to type II collagen-expressing tissues, confirmed by Southern blotting, DNA sequencing, and mRNA hybridization. Southern blotting, DNA sequencing, mRNA hybridization, somatic cell hybrid panel Proceedings of the National Academy of Sciences of the United States of America High 3857598 6594770
1991 Expression of a partially deleted COL2A1 minigene in transgenic mice produces chondrodysplasia via procollagen suicide: shortened pro-alpha1(II) chains form disulfide-linked heterotrimers with normal chains, causing their co-degradation and depletion of endogenous type II procollagen. Transgenic mouse generation, cultured chondrocyte biochemical analysis, disulfide-linked chain electrophoresis Proceedings of the National Academy of Sciences of the United States of America High 1881905
1991 The human COL2A1 gene can be expressed in mouse NIH 3T3 cells using a heterologous promoter, with correct post-translational processing; specific downstream sequences (3.5 kb SphI/SphI fragment) are required for proper transcription termination and 3' RNA processing. Recombinant expression in NIH 3T3 cells, Northern blotting, mRNA analysis The Journal of biological chemistry Medium 1860834
1992 A glycine-to-serine substitution at position 574 of COL2A1 (hypochondrogenesis) impairs conversion of type II procollagen to collagen, blocks intracellular transport and secretion, and disrupts collagen fibril assembly in cultured chondrocytes. Chondrocyte culture system (monolayer/agarose), PCR-cDNA scanning, SSCP, direct sequencing, electrophoretic collagen analysis, morphological assessment Proceedings of the National Academy of Sciences of the United States of America High 1374906
1997 Sox9 expression temporally precedes and colocalizes with Col2a1 expression in all chondroprogenitor cells during mouse embryonic development; Sox9 is absent in hypertrophic chondrocytes where Col2a1 is also reduced, establishing Sox9 as an upstream transcriptional regulator of Col2a1. In situ hybridization of mouse embryo sections at multiple developmental stages Developmental dynamics Medium 9264261
1998 A 48-bp enhancer in Col2a1 intron 1 contains three HMG-like binding sites (sites 1–3) all required for chondrocyte-specific expression in vivo; SOX9 binds site 3 and cooperates with other proteins binding sites 1 and 2 to form a large chondrocyte-specific nucleoprotein complex that drives cartilage-specific Col2a1 transcription. Transgenic mice (in vivo reporter), transient transfection, site-directed mutagenesis, electrophoretic mobility shift assay (EMSA) The Journal of biological chemistry High 9614106 9614107
1998 The Col11a2 chondrocyte-specific enhancers share HMG-like binding sites with the Col2a1 48-bp enhancer; both form similar DNA-protein complexes including SOX9, and SOX9 activates both enhancers in non-chondrocytic cells, indicating a shared SOX9-driven transcriptional program coordinates Col2a1 and Col11a2 expression in cartilage. EMSA, transient transfection, transgenic mice, SOX9 ectopic expression The Journal of biological chemistry High 9614107
2000 PKA (cAMP-dependent protein kinase A) phosphorylates SOX9 at two consensus sites (Ser64 and Ser211), enhancing its DNA-binding activity and its ability to transactivate the Col2a1 chondrocyte-specific 48-bp enhancer; PKA-Cα interacts directly with SOX9 (yeast two-hybrid), and phosphorylation-deficient SOX9 mutants show markedly reduced PKA-dependent enhancer activation. Yeast two-hybrid, in vitro kinase assay, phosphospecific antibody, cotransfection with PKA-Cα, mutagenesis of PKA sites, immunohistochemistry Molecular and cellular biology High 10805756
2001 Sp1 activates COL2A1 transcription through GC-box elements in the −266 to +121 bp promoter region; Sp3 does not activate COL2A1 alone but competitively blocks Sp1-driven transactivation. Both factors bind specifically to COL2A1 promoter sequences (DNase I footprinting, gel retardation). Sp1/Sp3 levels are reduced in dedifferentiated chondrocytes. Transient transfection of COL2A1 promoter deletion constructs, DNase I footprinting, gel retardation (EMSA), immunochemical analysis of Sp1/Sp3 levels The Journal of biological chemistry Medium 11447232
2001 Heterozygous knockout of Col2a1 in mice results in shorter limb bones, premature vertebral endplate ossification, reduced glycosaminoglycans in annulus fibrosus and endplates, with partial compensation by 15 months; establishing that a single functional Col2a1 allele is insufficient for normal early skeletal development. Heterozygous knockout mouse model, radiography, quantitative and polarized light microscopy, immunohistochemistry, in situ hybridization Spine Medium 11725236
2003 IFN-γ represses COL2A1 transcription through its TATA-containing core promoter (−45 to +11 bp) via a JAK1/JAK2/Stat1α-dependent mechanism; Stat1α is activated (phosphorylated at Tyr-701) and indirectly interacts with the general transcriptional machinery driving COL2A1 expression, without requiring a direct GAS element in the COL2A1 core promoter. Luciferase reporter constructs with COL2A1 promoter deletions, JAK-deficient cell lines (U4A, γ2A, U3A), dominant-negative Stat1α mutant, JAB overexpression, EMSA for Stat1α binding The Biochemical journal High 12223098
2003 SOX9 exerts a dose-dependent bifunctional effect on COL2A1 transcription: low SOX9 levels activate COL2A1 through the intronic enhancer, while high SOX9 levels repress COL2A1 through the −266 bp promoter region; in advanced chondrocyte dedifferentiation, SOX9 represses COL2A1 even through the −63 bp short promoter regardless of dose. Transient transfection of COL2A1 promoter/enhancer constructs in primary and passaged rabbit articular chondrocytes with graded SOX9 overexpression DNA and cell biology Medium 12713737
2007 Alternative splicing of COL2A1 pre-mRNA generates at least four isoforms (IIA, IIB, IIC, IID) in a developmentally regulated manner: IIA/IID (exon 2-containing) predominate in chondroprogenitors, while IIB (exon 2-excluded) predominates in differentiated chondrocytes; the IIC isoform uses an alternative 5' splice site producing a premature stop codon; deletion of the IIC splice site shifts the IIA:IIB ratio, indicating this alternative splice site regulates mRNA abundance. RT-PCR, Southern analysis, COL2A1 mini-gene splicing assays in cell lines Matrix biology Medium 18023161
2008 ESE-1 (ETS factor) is induced by IL-1β in chondrocytes and acts as a potent transcriptional repressor of COL2A1 by binding to tandem ETS sites at −403/−381 bp of the COL2A1 promoter; ESE-1 accounts for the sustained NF-κB-dependent inhibition of COL2A1 by IL-1β, while ETS-1 antagonizes this repression. ESE-1 binding to the COL2A1 promoter was confirmed in vivo by ChIP. Transient cotransfection, siRNA knockdown of ESE1/ETS1, ChIP, EMSA, promoter deletion analysis Journal of cellular physiology High 18044710
2012 Knock-in mice engineered to constitutively express the Col2a1 IIA exon 2-containing isoform (by strengthening the exon 2 5' splice site) produce only IIA mRNA in chondrocytes at all developmental stages, demonstrating the splice site sequence is the molecular switch controlling the IIA-to-IIB transition during chondrogenesis; homozygous mice are viable without overt phenotype, suggesting the IIA-to-IIB switch is not essential for gross skeletal development. Knock-in mouse model, mini-gene splicing assay, RT-PCR, isoform-specific protein detection at multiple developmental time points Matrix biology High 22248926
2012 Nkx3.2 directly binds the Col2a1 enhancer element (demonstrated by ChIP) and upregulates Col2a1 transcription independently of Sox9 in mesenchymal cells; Nkx3.2 also partially rescues Sox9 knockdown-induced loss of Col2a1 expression, indicating a Sox9-independent direct transcriptional activation pathway for Col2a1. Dual luciferase reporter assay, siRNA knockdown of Sox9 and Nkx3.2, ChIP, glycosaminoglycan quantification PloS one Medium 22511961
2013 Somatic mutations (insertions, deletions, rearrangements) in COL2A1 are found in 37% of chondrosarcomas, with patterns consistent with selection for variants impairing normal collagen biosynthesis, establishing COL2A1 loss-of-function as a driver event in chondrosarcoma. Comprehensive genomic analysis (whole-genome/exome sequencing) of 49 chondrosarcoma cases Nature genetics Medium 23770606
2014 Set7/9 (a histone methyltransferase) and SirT1 (a histone deacetylase) form a protein complex on the COL2A1 promoter in 3D-cultured chondrocytes; Set7/9 represses SirT1's deacetylase activity at this locus, resulting in enrichment of activating histone marks (H3K4me3, acetylated H3K9/14, H4K16), and morphology-dependent COL2A1 upregulation. Loss of Set7/9 from the promoter correlates with reduced COL2A1 expression during chondrocyte passaging. ChIP, ChIP-reChIP (co-occupancy), 3D alginate bead chondrocyte culture, immunochemistry for histone modifications Journal of bone and mineral research Medium 23873758
2016 ELF3 represses COL2A1 transcription by directly interacting with the HMG domain of SOX9 (demonstrated by co-transfection with truncated Sox9 fragments and Gal4-Sox9 reporter assay), inhibiting SOX9/CBP-p300-dependent histone acetyltransferase activity; ELF3 also inhibits Sox9-driven Col2a1 enhancer activity even at the 89-bp minimal enhancer lacking ELF3 direct binding sites. Co-transfection, Gal4-Sox9 reporter assay, HAT activity assay, domain mapping with truncated Sox9 fragments, promoter methylation analysis Connective tissue research Medium 27310669
2002 Transgenic mice expressing human COL2A1 with an Arg519Cys mutation develop skeletal defects (cleft palate, disorganized growth plate, reduced stature) and show dilated chondrocyte Golgi cisternae and decreased collagen fibril density in articular cartilage by electron microscopy, indicating the mutant protein is retained intracellularly and fails to assemble normal collagen fibrils. Transgenic mouse generation, histology, electron microscopy of articular cartilage Osteoarthritis and cartilage Medium 12359167
2021 CDC5L (cell division cycle 5-like splicing factor) directly binds Col2a1 and Sox9 pre-mRNA transcripts (RNA-binding protein immunoprecipitation) and is required for efficient pre-mRNA splicing of Col2a1 and Sox9 in chondrocytes; Cdc5l knockdown decreases Col2a1 mRNA and cartilage matrix production in murine chondrocytes and suppresses metatarsal cartilage rudiment growth. siRNA knockdown, shRNA knockdown, RT-PCR (splicing efficiency), RNA-binding protein immunoprecipitation (RIP), cartilage rudiment organ culture, FACS cell cycle analysis The Journal of biological chemistry Medium 34298017
1995 Intron 1 sequences of COL2A1 contribute differentially to transcriptional activity at different stages of chondrocyte differentiation: intronic sequences drive higher activity at onset of chondrogenesis than in mature chondrocytes, indicating distinct regulatory mechanisms operate in early versus fully differentiated chondrocytes. Transient transfection of COL2A1 promoter/intron reporter constructs in micromass cultures and sternal chondrocytes; transgenic mice Matrix biology Medium 8785590
2017 Col2a1-expressing progenitors contribute to osteoblasts and suture mesenchymal cells in the calvaria, in addition to chondrocytes, and to chondrocytes and osteoblasts in the mandibular condyle during growth phase; demonstrating that Col2a1-cre marks skeletal progenitors that contribute to multiple ossification modes in craniofacial development. Col2a1-Cre/R26R-tdTomato lineage tracing in mice, histological analysis of cranial base, calvaria, and mandibular condyle Orthodontics & craniofacial research Medium 28643905

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 413 9264261
2000 Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. Molecular and cellular biology 233 10805756
1998 Chondrocyte-specific enhancer elements in the Col11a2 gene resemble the Col2a1 tissue-specific enhancer. The Journal of biological chemistry 229 9614107
2013 Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma. Nature genetics 165 23770606
1998 Three high mobility group-like sequences within a 48-base pair enhancer of the Col2a1 gene are required for cartilage-specific expression in vivo. The Journal of biological chemistry 146 9614106
1985 Identification and characterization of the human type II collagen gene (COL2A1). Proceedings of the National Academy of Sciences of the United States of America 143 3857598
2012 Modeling colitis-associated cancer with azoxymethane (AOM) and dextran sulfate sodium (DSS). Journal of visualized experiments : JoVE 141 22990604
2010 Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients. European journal of human genetics : EJHG 120 20179744
1991 Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia. Proceedings of the National Academy of Sciences of the United States of America 117 1881905
2015 Mutation Update for COL2A1 Gene Variants Associated with Type II Collagenopathies. Human mutation 115 26443184
2010 Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. Human mutation 107 20513134
2000 COL2A1 exon 2 mutations: relevance to the Stickler and Wagner syndromes. The British journal of ophthalmology 102 10729292
1992 Characterization of a type II collagen gene (COL2A1) mutation identified in cultured chondrocytes from human hypochondrogenesis. Proceedings of the National Academy of Sciences of the United States of America 84 1374906
2013 Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis. PloS one 83 23861820
2001 Sp3 represses the Sp1-mediated transactivation of the human COL2A1 gene in primary and de-differentiated chondrocytes. The Journal of biological chemistry 80 11447232
2020 Quercetin Suppresses AOM/DSS-Induced Colon Carcinogenesis through Its Anti-Inflammation Effects in Mice. Journal of immunology research 72 32537472
2003 SOX9 exerts a bifunctional effect on type II collagen gene (COL2A1) expression in chondrocytes depending on the differentiation state. DNA and cell biology 71 12713737
2003 The Stickler syndrome: genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1. Genetics in medicine : official journal of the American College of Medical Genetics 69 12544472
2016 Molecular genetics of the COL2A1-related disorders. Mutation research. Reviews in mutation research 67 27234559
2003 Clinical variability of Stickler syndrome: role of exon 2 of the collagen COL2A1 gene. Survey of ophthalmology 64 12686304
2001 Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen. Spine 64 11725236
2000 Adjacent genes, for COL2A1 and the vitamin D receptor, are associated with separate features of radiographic osteoarthritis of the knee. Arthritis and rheumatism 60 10902746
2021 Emodin Inhibits Inflammation, Carcinogenesis, and Cancer Progression in the AOM/DSS Model of Colitis-Associated Intestinal Tumorigenesis. Frontiers in oncology 56 33489875
1995 Identification of COL2A1 gene mutations in patients with chondrodysplasias and familial osteoarthritis. Arthritis and rheumatism 54 7612049
2022 Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice via Modulating Inflammation and Intestinal Microbiota. Nutrients 53 35215376
2021 Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis. Frontiers in pharmacology 53 35002731
2014 Set7/9 impacts COL2A1 expression through binding and repression of SirT1 histone deacetylation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 50 23873758
2013 Microbiology of bacteria causing recurrent acute otitis media (AOM) and AOM treatment failure in young children in Spain: shifting pathogens in the post-pneumococcal conjugate vaccination era. International journal of pediatric otorhinolaryngology 49 23746414
2008 ESE-1 is a potent repressor of type II collagen gene (COL2A1) transcription in human chondrocytes. Journal of cellular physiology 46 18044710
2023 Astragaloside IV inhibits AOM/DSS-induced colitis-associated tumorigenesis via activation of PPARγ signaling in mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 45 37776619
2022 Lactiplantibacillus plantarum-12 Alleviates Inflammation and Colon Cancer Symptoms in AOM/DSS-Treated Mice through Modulating the Intestinal Microbiome and Metabolome. Nutrients 44 35565884
2011 Osteoarthritis-like changes in the heterozygous sedc mouse associated with the HtrA1-Ddr2-Mmp-13 degradative pathway: a new model of osteoarthritis. Osteoarthritis and cartilage 44 22155431
2010 Genetic variants in COL2A1, COL11A2, and IRF6 contribute risk to nonsyndromic cleft palate. Birth defects research. Part A, Clinical and molecular teratology 43 20672350
2003 The TATA-containing core promoter of the type II collagen gene (COL2A1) is the target of interferon-gamma-mediated inhibition in human chondrocytes: requirement for Stat1 alpha, Jak1 and Jak2. The Biochemical journal 43 12223098
2017 Ceramide synthase 2 deficiency aggravates AOM-DSS-induced colitis in mice: role of colon barrier integrity. Cellular and molecular life sciences : CMLS 42 28405720
1988 Structural and segregation analysis of the type II collagen gene (COL2A1) in some heritable chondrodysplasias. Journal of medical genetics 40 2902229
2019 Integrated analysis of COL2A1 variant data and classification of type II collagenopathies. Clinical genetics 39 31758797
2014 A novel p. Gly630Ser mutation of COL2A1 in a Chinese family with presentations of Legg-Calvé-Perthes disease or avascular necrosis of the femoral head. PloS one 39 24949742
1993 Characterization of the COL2A1 VNTR polymorphism. Genomics 39 8314574
2008 Exclusion of COL2A1 and VDR as developmental dysplasia of the hip genes. Clinical orthopaedics and related research 38 18288556
2013 Osteoarthritis in temporomandibular joint of Col2a1 mutant mice. Archives of oral biology 37 23518238
2016 ELF3 modulates type II collagen gene (COL2A1) transcription in chondrocytes by inhibiting SOX9-CBP/p300-driven histone acetyltransferase activity. Connective tissue research 35 27310669
2005 A novel mutation of COL2A1 resulting in dominantly inherited rhegmatogenous retinal detachment. Investigative ophthalmology & visual science 35 15671297
2017 Association of gene variants of transcription factors PPARγ, RUNX2, Osterix genes and COL2A1, IGFBP3 genes with the development of osteonecrosis of the femoral head in Chinese population. Bone 33 28476574
2014 Analysis of the association of COL2A1 and IGF-1 with mandibular prognathism in a Chinese population. Orthodontics & craniofacial research 33 24386886
1991 Expression of a human cartilage procollagen gene (COL2A1) in mouse 3T3 cells. The Journal of biological chemistry 33 1860834
2011 Identification of three novel mutations in the COL2A1 gene in four unrelated Chinese families with spondyloepiphyseal dysplasia congenita. Biochemical and biophysical research communications 31 21924244
2009 A permease encoded by STL1 is required for active glycerol uptake by Candida albicans. Microbiology (Reading, England) 31 19383674
1984 Localization of human type II procollagen gene (COL2A1) to chromosome 12. Somatic cell and molecular genetics 31 6594770
2012 Mutation-based growth charts for SEDC and other COL2A1 related dysplasias. American journal of medical genetics. Part C, Seminars in medical genetics 29 22791362
2002 Skeletal abnormalities and ultrastructural changes of cartilage in transgenic mice expressing a collagen II gene (COL2A1) with a Cys for Arg-alpha1-519 substitution. Osteoarthritis and cartilage 29 12359167
2021 Co-administration of 5FU and propolis on AOM/DSS induced colorectal cancer in BALB-c mice. Life sciences 27 33794252
2022 Theabrownin Alleviates Colorectal Tumorigenesis in Murine AOM/DSS Model via PI3K/Akt/mTOR Pathway Suppression and Gut Microbiota Modulation. Antioxidants (Basel, Switzerland) 26 36139789
1995 Human COL2A1-directed SV40 T antigen expression in transgenic and chimeric mice results in abnormal skeletal development. The Journal of cell biology 26 7822417
2022 Supplementation of quinoa peptides alleviates colorectal cancer and restores gut microbiota in AOM/DSS-treated mice. Food chemistry 25 36535178
2015 Human articular chondrocytes with higher aldehyde dehydrogenase activity have stronger expression of COL2A1 and SOX9. Osteoarthritis and cartilage 25 26687820
2007 Expression of two novel alternatively spliced COL2A1 isoforms during chondrocyte differentiation. Matrix biology : journal of the International Society for Matrix Biology 25 18023161
2003 Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. Investigative ophthalmology & visual science 25 12939326
1995 Differential allelic expression of the type II collagen gene (COL2A1) in osteoarthritic cartilage. American journal of human genetics 25 7726176
1994 The STL1 gene of Saccharomyces cerevisiae is predicted to encode a sugar transporter-like protein. Gene 25 8076821
2012 Somatic mosaicism and the phenotypic expression of COL2A1 mutations. American journal of medical genetics. Part A 24 22496037
2012 Nkx3.2 promotes primary chondrogenic differentiation by upregulating Col2a1 transcription. PloS one 24 22511961
2022 T-Cell-Specific CerS4 Depletion Prolonged Inflammation and Enhanced Tumor Burden in the AOM/DSS-Induced CAC Model. International journal of molecular sciences 22 35163788
2017 Novel and recurrent COL11A1 and COL2A1 mutations in the Marshall-Stickler syndrome spectrum. Human genome variation 22 28983407
2020 Aom2 S: A new web-based application for DNA/RNA tandem mass spectrometry data interpretation. Rapid communications in mass spectrometry : RCM 21 32812285
2020 Skeletal deterioration in COL2A1-related spondyloepiphyseal dysplasia occurs prior to osteoarthritis. Osteoarthritis and cartilage 20 31958497
2017 Boswellia serrata resin extract alleviates azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis. Molecular nutrition & food research 20 28245338
2006 Precocious osteoarthritis in a family with recurrent COL2A1 mutation. The Journal of rheumatology 20 16755660
2003 Anti-PsaA and the risk of pneumococcal AOM and carriage. Vaccine 20 12922089
2023 ENPP2 inhibitor improves proliferation in AOM/DSS-induced colorectal cancer mice via remodeling the gut barrier function and gut microbiota composition. Pharmacological research 19 37524154
2016 Novel mutations in the COL2A1 gene in Japanese patients with Stickler syndrome. Human genome variation 19 27408751
2007 Glucose repression over Saccharomyces cerevisiae glycerol/H+ symporter gene STL1 is overcome by high temperature. FEBS letters 19 17434487
2004 A human COL2A1 gene with an Arg519Cys mutation causes osteochondrodysplasia in transgenic mice. Arthritis and rheumatism 19 15476249
2020 A novel deep intronic COL2A1 mutation in a family with early-onset high myopia/ocular-only Stickler syndrome. Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) 18 32196734
2017 Disinfection by-product formation during chlor(am)ination of algal organic matters (AOM) extracted from Microcystis aeruginosa: effect of growth phases, AOM and bromide concentration. Environmental science and pollution research international 18 28188554
2007 Stickler and branchio-oto-renal syndromes in a patient with mutations in EYA1 and COL2A1 genes. Clinical genetics 18 18177466
2023 Electroacupuncture ameliorates AOM/DSS-induced mice colorectal cancer by inhibiting inflammation and promoting autophagy via the SIRT1/miR-215/Atg14 axis. Aging 17 38006398
2022 Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model. Cancer research and treatment 17 35790194
2021 Safflower Polysaccharide Inhibits AOM/DSS-Induced Mice Colorectal Cancer Through the Regulation of Macrophage Polarization. Frontiers in pharmacology 17 34744741
2018 Probing algogenic organic matter (AOM) by size-exclusion chromatography to predict AOM-derived disinfection by-product formation. The Science of the total environment 17 30015120
2017 Diverse contribution of Col2a1-expressing cells to the craniofacial skeletal cell lineages. Orthodontics & craniofacial research 17 28643905
2015 Identification of a Novel Mutation in the COL2A1 Gene in a Chinese Family with Spondyloepiphyseal Dysplasia Congenita. PloS one 17 26030151
2012 Disruption of the developmentally-regulated Col2a1 pre-mRNA alternative splicing switch in a transgenic knock-in mouse model. Matrix biology : journal of the International Society for Matrix Biology 17 22248926
2024 Integration of microbiome, metabolomics and transcriptome for in-depth understanding of berberine attenuates AOM/DSS-induced colitis-associated colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 39151314
2019 Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia. American journal of medical genetics. Part A 16 30740902
2014 Association of COL2A1 gene polymorphism with degenerative lumbar scoliosis. Clinics in orthopedic surgery 16 25436060
2022 Andean berry (Vaccinium meridionale Swartz) juice, in combination with Aspirin, displayed antiproliferative and pro-apoptotic mechanisms in vitro while exhibiting protective effects against AOM-induced colorectal cancer in vivo. Food research international (Ottawa, Ont.) 15 35761556
2022 6- shogaol suppresses AOM/DSS-mediated colorectal adenoma through its antioxidant and anti-inflammatory effects in mice. Journal of food biochemistry 15 36125935
2021 CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1. The Journal of biological chemistry 15 34298017
2021 Protective effect of Pai-Nong-San against AOM/DSS-induced CAC in mice through inhibiting the Wnt signaling pathway. Chinese journal of natural medicines 15 34961589
2022 Lactobacillus kefiranofaciens JKSP109 and Saccharomyces cerevisiae JKSP39 isolated from Tibetan kefir grain co-alleviated AOM/DSS induced inflammation and colorectal carcinogenesis. Food & function 14 35575226
2018 The association between different molecular weights of hyaluronic acid and CHAD, HIF-1α, COL2A1 expression in chondrocyte cultures. Experimental and therapeutic medicine 14 29849772
2015 The yeast Hot1 transcription factor is critical for activating a single target gene, STL1. Molecular biology of the cell 14 25904326
2022 Synergistic Effect of Huangqin Decoction Combined Treatment With Radix Actinidiae chinensis on DSS and AOM-Induced Colorectal Cancer. Frontiers in pharmacology 13 35873550
2021 Suppression of C-C chemokine receptor 1 is a key regulation for colon cancer chemoprevention in AOM/DSS mice by fucoxanthin. The Journal of nutritional biochemistry 13 34571188
2019 Salivary Glycine Is a Significant Predictor for the Attenuation of Polyp and Tumor Microenvironment Formation by Fucoxanthin in AOM/DSS Mice. In vivo (Athens, Greece) 13 30804114
2018 Cannabinoid Receptor-1 Up-regulation in Azoxymethane (AOM)-treated Mice After Dietary Treatment with Quercetin. Anticancer research 13 30061214
2016 Characterization of genetically engineered mouse models carrying Col2a1-cre-induced deletions of Lrp5 and/or Lrp6. Bone research 13 26962465
2013 Structural variations in articular cartilage matrix are associated with early-onset osteoarthritis in the spondyloepiphyseal dysplasia congenita (sedc) mouse. International journal of molecular sciences 13 23939426
1995 Differential regulation of COL2A1 expression in developing and mature chondrocytes. Matrix biology : journal of the International Society for Matrix Biology 12 8785590