Collagen alpha-1(II) chain · UniProt P02458
COL2A1 encodes the α1 chain of type II collagen, the major structural collagen whose proper assembly is essential for the integrity of cartilaginous skeletal elements, the trachea, the vitreous, and the inner ear, as shown by loss-of-function CRISPR/Cas9 swine that develop severe skeletal dysplasia and lethal tracheal collapse (PMID:32450343). Its chondrocyte-specific transcription is governed by a 48-bp intron 1 enhancer carrying three HMG-like sites at which SOX9 binds and bends DNA to nucleate a chondrocyte-specific protein-DNA complex (PMID:9614106, PMID:9614107), with SOX9 expression preceding and tracking COL2A1 throughout chondrogenesis (PMID:9264261). This enhancer integrates additional inputs: Nkx3.2 binds it and activates transcription both SOX9-dependently and independently (PMID:22511961), and mechanical (cyclic tensile) strain drives TGF-β1/Smad2/3 signaling that forms a Smad-SOX9 complex on the enhancer (PMID:23631855), while SP1 activates the core promoter through GC-rich sites antagonized by SP3 (PMID:11447232). Transcription is repressed by IFN-γ acting through JAK1/JAK2/STAT1α on the TATA-containing core promoter (PMID:12223098) and by ELF3, which binds the SOX9 HMG domain and inhibits SOX9/CBP-p300 HAT activity (PMID:27310669), whereas a Set7/9–SirT1 complex on the promoter biases histone marks toward activation (PMID:23873758). COL2A1 pre-mRNA undergoes developmentally regulated alternative splicing of exon 2 — producing the cysteine-rich type IIA isoform versus the mature type IIB isoform — controlled by TIA-1 binding an AU-rich intronic element (PMID:17580305), by the strength of the exon 2 5' splice site (PMID:22248926), and by CDC5L, which directly promotes COL2A1 and SOX9 pre-mRNA splicing (PMID:34298017). Dominant-negative glycine/arginine-to-cysteine substitutions in the triple-helical domain (e.g. Arg519Cys, Arg1417Cys) disrupt collagen II fibril assembly and secretion, reducing fibril density, dilating chondrocyte Golgi, and causing spondyloepiphyseal dysplasia, osteoarthritis, and disc degeneration in a dose-dependent manner (PMID:12359167, PMID:15476249, PMID:12968670, PMID:23939426, PMID:22155431), while exon-2-restricted and haploinsufficiency-type variants produce predominantly ocular Stickler syndrome (PMID:7726176, PMID:32196734).
Establishing the chromosomal location of the type II procollagen gene was the prerequisite for all subsequent genetic and regulatory dissection.
Evidence Southern blot of human-mouse somatic cell hybrids
Defined that correct COL2A1 transcript termination and 3' processing require specific downstream genomic sequences, addressing how the gene's mRNA is properly bounded.
Evidence Recombinant expression of human COL2A1 in NIH 3T3 cells with deletion constructs and Northern blot
Revealed that COL2A1 mRNA is expressed beyond chondrocytes in the cochlea while protein is restricted to connective-tissue structures, implicating post-transcriptional control in the inner ear.
Evidence Northern blot, in situ hybridization, and immunohistochemistry on human fetal cochlea
Proposed that reduced COL2A1 allelic expression predisposes to osteoarthritis, linking quantitative expression to disease, and that regulatory mechanisms differ between differentiating and mature chondrocytes.
Evidence Allele-specific mRNA quantification in OA cartilage; reporter constructs in micromass and sternal chondrocytes
Identified the chondrocyte-specific 48-bp intron 1 enhancer with three HMG sites and showed SOX9 binds and bends site 3, defining the core cis-regulatory module driving tissue-specific expression.
Evidence Transgenic mice with enhancer mutagenesis, transient transfection, EMSA
Demonstrated spatiotemporal coupling of SOX9 and COL2A1 expression through chondrogenesis, supporting SOX9 as the direct in vivo driver.
Evidence In situ hybridization comparing Sox9 and Col2a1 across embryonic stages
Showed SP1 activates the COL2A1 core promoter while SP3 competitively represses, identifying a tunable activator/repressor balance at GC-rich promoter sequences.
Evidence Promoter-luciferase deletions, DNase I footprinting, gel retardation, SP1/SP3 overexpression
Mapped IFN-γ repression of COL2A1 to the JAK1/JAK2/STAT1α pathway acting on the core TATA promoter, defining a cytokine-driven off-switch operating indirectly through general transcription machinery.
Evidence Luciferase deletion constructs, JAK-deficient cell lines, dominant-negative STAT1α in human chondrocytes
Demonstrated in vivo that the Arg519Cys triple-helical mutation impairs collagen II fibril assembly and secretion, providing the first transgenic structural evidence for dominant disruption.
Evidence Transgenic mice, electron microscopy and histology of cartilage and growth plate
Established that a single triple-helical Arg-to-Cys substitution (mouse Arg1417Cys / human Arg789Cys) is sufficient to cause combined skeletal, ocular, and auditory disease.
Evidence Positional mapping and sequencing of sedc mice with phenotypic characterization
Demonstrated dose-dependent dominant-negative pathology of Arg519Cys, showing the mutant allele disrupts the collagen network more severely when no normal allele is present.
Evidence Mice with defined allele combinations, radiography, histology, TEM
Identified TIA-1 as a dual DNA/RNA-binding regulator of exon 2 alternative splicing via a conserved AU-rich intronic element, coupling transcription and splicing of COL2A1.
Evidence Mini-gene splicing assay, RIP, ChIP with RNase step, competition binding
Discovered additional alternatively spliced isoforms (IIC, IID) during MSC chondrogenesis and showed the IIC splice site influences the IIA:IIB ratio, refining the splicing landscape.
Evidence RT-PCR, Southern blot, mini-gene mutagenesis in differentiating MSCs
Linked exon-2-specific mutations to predominantly ocular Stickler syndrome, providing genotype-phenotype evidence that the IIA-specific domain underlies vitreous-restricted pathology.
Evidence Pedigree linkage and sequencing of all 54 COL2A1 exons across 8 families
Showed Nkx3.2 directly binds the enhancer and activates COL2A1 both dependently and independently of SOX9, broadening the transcriptional input network.
Evidence ChIP, dual luciferase reporter, Sox9 RNAi with Nkx3.2 rescue in chondrogenic cell lines
Established with a knock-in mouse that forced constitutive IIA splicing is non-lethal, showing the IIA-to-IIB switch is dispensable for survival though it leaves the cysteine-rich domain ectopically present.
Evidence Splice-site knock-in mouse with developmental RT-PCR and Western time-course
Connected mechanical loading to COL2A1 transcription via TGF-β1/Smad2/3 forming a complex with SOX9 on the enhancer, defining a mechanotransduction input.
Evidence ChIP, co-IP of Smad2/3 and SOX9, reporter assays, mechanical stretching of SW1353 cells
Defined a degradative pathway (HtrA1, Ddr2, Mmp-13) upregulated downstream of the mutant Arg1417Cys collagen prior to cartilage fibrillation, linking mutant collagen structure to OA initiation.
Evidence OARSI histomorphometry, IHC, and EM in sedc mice across ages
Showed Set7/9 forms a complex with SirT1 on the COL2A1 promoter to block deacetylation and elevate activating histone marks, defining epigenetic activation of the gene.
Evidence ChIP and ChIP-reChIP in 3D-cultured chondrocytes with RT-PCR
Identified ELF3 as a repressor that binds the SOX9 HMG domain and inhibits SOX9/CBP-p300 HAT activity, defining a protein-protein mechanism that dampens COL2A1 transcription.
Evidence Reporter assays, Gal4-Sox9 assay, co-IP domain mapping, HAT activity assay
Demonstrated via CRISPR/Cas9 swine that COL2A1 loss of function is essential for skeletal and tracheal cartilage integrity, with neonatal lethality from tracheal collapse.
Evidence CRISPR/Cas9 with SCNT to generate mutant piglets, skeletal and histological phenotyping
Showed a deep intronic variant creating a cryptic splice acceptor causes ocular-only Stickler syndrome, extending the spectrum of pathogenic splicing defects.
Evidence Linkage scan, Sanger sequencing, ex vivo mini-gene splicing assay
Identified CDC5L as a direct binder of COL2A1 and SOX9 pre-mRNA promoting their splicing, coupling splicing fidelity to chondrocyte matrix production and cell cycle control.
Evidence RIP, siRNA/shRNA knockdown, FACS cell cycle analysis, cartilage rudiment culture
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 1998 | A 48-bp enhancer element in COL2A1 intron 1 contains three HMG-like binding sites (sites 1-3) that are each required for chondrocyte-specific expression in vivo; SOX9 binds site 3 and bends DNA at that site, while all three sites cooperatively form a large chondrocyte-specific protein-DNA complex with SOX9 and other proteins. | Transgenic mice with site-directed mutagenesis of enhancer elements, transient transfections, electrophoretic mobility shift assay (EMSA) | The Journal of biological chemistry | High | 9614106 9614107 |
| 1997 | SOX9 expression precedes and co-localizes with COL2A1 expression in all chondroprogenitor cells during mouse embryonic development, and high SOX9 levels correlate with high COL2A1 levels in chondrocytes; SOX9 expression is absent in hypertrophic chondrocytes where COL2A1 levels are low, consistent with SOX9 directly driving COL2A1 expression via the chondrocyte-specific enhancer. | In situ hybridization comparing Sox9 and Col2a1 expression patterns across embryonic stages in transgenic mice | Developmental dynamics | Medium | 9264261 |
| 2001 | SP1 activates COL2A1 promoter transcription by binding specific GC-rich cis-sequences in the -266 to +121 bp region; SP3 competes for the same sites and represses SP1-mediated transactivation without independently activating transcription. SP1/SP3 ratio and cooperation with other transcription factors determines chondrocyte-specific COL2A1 expression. | Transient transfection with deleted COL2A1 promoter-luciferase constructs, DNase I footprinting, gel retardation assays, overexpression of SP1/SP3 in differentiated and de-differentiated chondrocytes | The Journal of biological chemistry | High | 11447232 |
| 2003 | IFN-γ suppresses COL2A1 transcription through the JAK1/JAK2/STAT1α pathway; the repression maps to the TATA-containing core promoter (-45 to +11 bp) and involves indirect interaction of activated STAT1α with the general transcriptional machinery rather than direct STAT1 binding to the COL2A1 promoter. | Luciferase reporter assays with deletion constructs, JAK-deficient cell lines (U4A, γ2A, U3A), dominant-negative STAT1α, JAK inhibitor (JAB) overexpression in human chondrocyte cell line C-28/I2 | The Biochemical journal | High | 12223098 |
| 2007 | RNA-binding protein TIA-1 binds a conserved AU-rich cis-element in COL2A1 intron 2 and modulates alternative splicing of exon 2; TIA-1 also interacts with the equivalent single-stranded DNA sequence in vivo (confirmed by ChIP), and active transcription by RNA polymerase disrupts TIA-1 DNA binding, suggesting a dual role in co-regulating COL2A1 at transcription and pre-mRNA splicing levels. | Mini-gene splicing assay, ribonucleoprotein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) with RNase step, competition binding assays | The Journal of biological chemistry | High | 17580305 |
| 2013 | Cyclic tensile strain (CTS) induces TGF-β1 secretion in human chondrocytic SW1353 cells, which activates Smad2/3 phosphorylation and nuclear translocation; phosphorylated Smad2/3 forms a complex with SOX9 and both bind to the COL2A1 enhancer (confirmed by ChIP), cooperatively driving COL2A1 expression. | Chromatin immunoprecipitation (ChIP), co-immunoprecipitation of Smad2/3 and SOX9, luciferase reporter assay with CCN2 and COL2A1 enhancer constructs, mechanical stretching apparatus | Journal of biomechanics | Medium | 23631855 |
| 2014 | Set7/9 histone methyltransferase forms a protein complex with SirT1 on the COL2A1 promoter (confirmed by ChIP-reChIP) and prevents SirT1's histone deacetylase activity, resulting in elevated trimethylated H3K4 (a Set7/9 activity mark) and acetylated H3K9/14 and H4K16, thereby promoting COL2A1 transcription in 3D-cultured chondrocytes. | Chromatin immunoprecipitation (ChIP and ChIP-reChIP), 3D alginate bead chondrocyte cultures, RT-PCR for COL2A1 mRNA | Journal of bone and mineral research | Medium | 23873758 |
| 2016 | ELF3 represses SOX9-driven COL2A1 transcription by directly interacting with the HMG domain of SOX9 and inhibiting SOX9/CBP-p300-dependent histone acetyltransferase (HAT) activity; ELF3 also reduces basal and SOX9-driven activity from the 4x48 enhancer construct lacking ELF3 binding sites, indicating the mechanism is through SOX9 interaction rather than direct promoter binding alone. | Co-transfection reporter assays (pGL2B-COL2A1 and pLuc-4x48), Gal4-Sox9 reporter assay, co-immunoprecipitation with truncated SOX9 fragments, HAT activity assay | Connective tissue research | Medium | 27310669 |
| 2012 | Nkx3.2 directly binds to the Col2a1 enhancer element (confirmed by ChIP) and upregulates Col2a1 transcription independently of Sox9, in addition to its previously described Sox9-dependent mechanism; partial rescue of Sox9 RNAi-induced Col2a1 suppression by Nkx3.2 overexpression confirms a Sox9-independent direct pathway. | ChIP assay, dual luciferase reporter assays with Col2a1 enhancer, RNAi knockdown of Sox9 with Nkx3.2 rescue, overexpression in C3H10T1/2 and N1511 cells | PloS one | Medium | 22511961 |
| 2007 | Two novel alternatively spliced COL2A1 isoforms (IIC and IID) are expressed during chondrocyte differentiation from mesenchymal stem cells: IIC uses an alternative 5' splice site retaining only 34 nt of exon 2, introducing a premature stop codon and likely triggering nonsense-mediated decay; IID uses another 5' splice site in intron 2 inserting one additional amino acid. Mutation of the IIC splice site increases the IIA:IIB ratio, indicating this site influences isoform balance. | RT-PCR, Southern blot, mini-gene mutagenesis in differentiating rabbit and human MSCs | Matrix biology | Medium | 18023161 |
| 2012 | Conversion of the Col2a1 exon 2 5' splice site from a weak non-consensus to a strong consensus sequence in a knock-in mouse forces constitutive retention of exon 2 (IIA isoform only) at all developmental stages. Homozygous Col2a1(+ex2) mice are viable with no overt phenotype, indicating the developmentally regulated IIA-to-IIB splicing switch is not essential for survival but the IIA-encoded cysteine-rich domain persists ectopically in post-natal cartilage. | Knock-in mouse model with splice-site mutation, RT-PCR and Western blot analysis across developmental stages (E12.5 to P70) | Matrix biology | Medium | 22248926 |
| 2021 | CDC5L binds directly to Col2a1 and Sox9 pre-mRNA transcripts (shown by RNA-binding protein immunoprecipitation) and promotes their splicing efficiency; Cdc5l siRNA decreases Col2a1 and Sox9 pre-mRNA splicing, reduces cartilage matrix production, and conversely enhances splicing of Wee1 pre-mRNA, leading to G2/M cell cycle arrest in chondrocytes. | RNA-binding protein immunoprecipitation (RIP), siRNA knockdown, FACS cell cycle analysis, cartilage rudiment culture with shRNA, RT-PCR for splicing efficiency | The Journal of biological chemistry | Medium | 34298017 |
| 2002 | Expression of the Arg519Cys mutant human COL2A1 in transgenic mice causes reduced collagen II fibril density in articular cartilage (by electron microscopy), dilated chondrocyte Golgi cisternae, disorganized growth plate, cleft palate, and skeletal retardation, demonstrating that this mutation impairs collagen II fibril assembly and secretion. | Transgenic mouse generation, electron microscopy of articular cartilage, histological analysis of growth plate | Osteoarthritis and cartilage | Medium | 12359167 |
| 2003 | A missense mutation in mouse Col2a1 (Arg1417Cys, equivalent to human Arg789Cys) causes spondyloepiphyseal dysplasia congenita with shortened trunk, dysplastic long bones and vertebrae, retinoschisis, and hearing loss, establishing that this single amino acid change in the triple-helical domain is sufficient to disrupt skeletal, ocular, and auditory development. | Positional mapping to Chr15, Sanger sequencing of Col2a1, phenotypic characterization of homozygous sedc mice | Journal of bone and mineral research | Medium | 12968670 |
| 2004 | Introduction of the human COL2A1 Arg519Cys mutation into mice replacing one or both normal Col2a1 alleles causes dysplastic long bones, flattened vertebrae, osteoarthritic joint changes, and intervertebral disc degeneration in a dose-dependent manner (worse with no normal allele), demonstrating dominant-negative disruption of cartilage collagen network by this mutation. | Transgenic mouse generation with defined allele combinations, radiographic imaging, histological sections, transmission electron microscopy of cartilage | Arthritis and rheumatism | Medium | 15476249 |
| 1991 | Heterologous expression of the human COL2A1 gene in mouse NIH 3T3 cells demonstrated that specific sequences in a downstream 3.5 kb SphI/SphI fragment are required for correct transcription termination and 3' processing of COL2A1 RNA transcripts; sequences 80 bp beyond the polyadenylation signal are not sufficient for this function. | Recombinant expression in NIH 3T3 cells, Northern blot analysis comparing mRNA levels and termination from two constructs differing in downstream sequences | The Journal of biological chemistry | Medium | 1860834 |
| 1984 | The human type II procollagen gene (COL2A1) was mapped to chromosome 12 by Southern blot analysis of human-mouse somatic cell hybrids. | Southern blot hybridization of 39 human-mouse somatic cell hybrid lines with human COL2A1 probe | Somatic cell and molecular genetics | Medium | 6594770 |
| 1994 | COL2A1 mRNA is expressed in multiple cell types of the human fetal cochlea beyond chondrocytes, including sensory hair cells, stria vascularis, spiral limbus, and spiral ligament cells; however, type II collagen protein is restricted to connective tissue structures (tectorial membrane, basilar membrane, spiral ligament), indicating post-transcriptional regulation in non-connective tissue cochlear cells. | Northern blot analysis, in situ hybridization, immunohistochemistry on human fetal cochlear sections | Hearing research | Medium | 7806485 |
| 2020 | A novel deep intronic COL2A1 variant (c.86-50C>G in intron 1) creates a new splice acceptor 49 bp upstream of the canonical exon 2 splice site, resulting in insertion of a 49 bp intronic fragment and premature termination, causing ocular-only Stickler syndrome. This was confirmed by ex vivo mini-gene splicing assay. | Linkage scan, Sanger sequencing, mini-gene ex vivo splicing assay | Ophthalmic & physiological optics | Medium | 32196734 |
| 2000 | Mutations specifically in exon 2 of COL2A1 produce a predominantly ocular Stickler syndrome phenotype with minimal systemic involvement, consistent with exon 2 encoding a domain present in the vitreous-specific type IIA procollagen isoform but absent from the adult cartilage type IIB isoform due to alternative splicing. | Pedigree linkage analysis, direct DNA sequencing of all 54 COL2A1 exons, genotype-phenotype correlation across 8 families | The British journal of ophthalmology | Medium | 10729292 |
| 1995 | Differential allelic expression of COL2A1 was identified in osteoarthritic cartilage; three OA patients heterozygous for COL2A1 coding dimorphisms showed <12% mRNA from one allele, and the same under-expressed allele was more frequent in an OA patient cohort, suggesting a rare COL2A1 allele that reduces expression predisposes to osteoarthritis. | Allele-specific mRNA quantification using coding region dimorphisms as allelic markers in cartilage RNA from OA patients | American journal of human genetics | Low | 7726176 |
| 1995 | The mechanisms regulating COL2A1 expression in newly differentiating chondrocytes differ from those maintaining expression in mature chondrocytes: a 5-kbp genomic fragment (including 1.8 kbp promoter, exon 1, and 3 kbp intron 1) drives high reporter activity at onset of chondrogenesis but activity declines in mature chondrocytes despite sustained endogenous mRNA. Intronic sequences are more critical for expression in differentiating than in mature chondrocytes. | Transient transfection of COL2A1-reporter constructs in micromass cultures, comparison with sternal chondrocytes, transgenic mouse expression analysis | Matrix biology | Low | 8785590 |
| 2013 | The sedc/sedc mouse (homozygous Col2a1 Arg1417Cys missense mutation) shows decreased collagen II fibril diameter, enlarged pericellular space, and early-onset knee osteoarthritis with increased OARSI scores; heterozygous sedc/+ mice develop OA preceded by upregulation of HtrA1, Ddr2, and Mmp-13 in articular cartilage before fibrillation occurs, implicating this degradative pathway downstream of mutant COL2A1. | Histomorphometry (modified Mankin/OARSI scoring), immunohistochemistry for HtrA1/Ddr2/Mmp-13, electron microscopy for fibril diameter measurement in sedc mouse cartilage | International journal of molecular sciences | Medium | 22155431 23939426 |
| 2020 | A CRISPR/Cas9-engineered swine model with COL2A1 loss-of-function mutations recapitulates severe skeletal dysplasia (shortened long bones, abnormal vertebrae, cleft palate, depressed nasal bridge) and tracheal collapse causing neonatal death, establishing that COL2A1 is essential for cartilaginous structural integrity of the trachea and skeletal elements in a large mammal. | CRISPR/Cas9 gene editing combined with somatic cell nuclear transfer to generate COL2A1 mutant piglets; skeletal and histological phenotyping | Bone | Medium | 32450343 |
| 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 |
| 2011 | Characterization of intracellular & extracellular algae organic matters (AOM) of Microcystic aeruginosa and formation of AOM-associated disinfection byproducts and odor & taste compounds. | Water research | 254 | 22209198 |
| 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 | 167 | 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 | 122 | 20179744 |
| 2015 | Mutation Update for COL2A1 Gene Variants Associated with Type II Collagenopathies. | Human mutation | 117 | 26443184 |
| 2010 | Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. | Human mutation | 112 | 20513134 |
| 2000 | COL2A1 exon 2 mutations: relevance to the Stickler and Wagner syndromes. | The British journal of ophthalmology | 102 | 10729292 |
| 2001 | Stage-and tissue-specific expression of a Col2a1-Cre fusion gene in transgenic mice. | Matrix biology : journal of the International Society for Matrix Biology | 88 | 11223335 |
| 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 |
| 2014 | Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma. | Genome research | 77 | 25024164 |
| 2020 | Quercetin Suppresses AOM/DSS-Induced Colon Carcinogenesis through Its Anti-Inflammation Effects in Mice. | Journal of immunology research | 74 | 32537472 |
| 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 | 65 | 12686304 |
| 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 |
| 2003 | A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis. | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research | 53 | 12968670 |
| 2013 | Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-β-Smad2/3 pathway in chondrocytic cells. | Journal of biomechanics | 52 | 23631855 |
| 2023 | Astragaloside IV inhibits AOM/DSS-induced colitis-associated tumorigenesis via activation of PPARγ signaling in mice. | Phytomedicine : international journal of phytotherapy and phytopharmacology | 50 | 37776619 |
| 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 |
| 2022 | Lactiplantibacillus plantarum-12 Alleviates Inflammation and Colon Cancer Symptoms in AOM/DSS-Treated Mice through Modulating the Intestinal Microbiome and Metabolome. | Nutrients | 49 | 35565884 |
| 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 |
| 2009 | COL1A1 and COL2A1 genes and myopia susceptibility: evidence of association and suggestive linkage to the COL2A1 locus. | Investigative ophthalmology & visual science | 45 | 19387081 |
| 2017 | Ceramide synthase 2 deficiency aggravates AOM-DSS-induced colitis in mice: role of colon barrier integrity. | Cellular and molecular life sciences : CMLS | 44 | 28405720 |
| 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 |
| 2019 | Integrated analysis of COL2A1 variant data and classification of type II collagenopathies. | Clinical genetics | 40 | 31758797 |
| 1988 | Structural and segregation analysis of the type II collagen gene (COL2A1) in some heritable chondrodysplasias. | Journal of medical genetics | 40 | 2902229 |
| 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 |
| 2007 | Nuclear protein TIA-1 regulates COL2A1 alternative splicing and interacts with precursor mRNA and genomic DNA. | The Journal of biological chemistry | 37 | 17580305 |
| 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 |
| 2014 | Analysis of the association of COL2A1 and IGF-1 with mandibular prognathism in a Chinese population. | Orthodontics & craniofacial research | 33 | 24386886 |
| 2004 | Childhood-onset osteoarthritis, tall stature, and sensorineural hearing loss associated with Arg75-Cys mutation in procollagen type II gene (COL2A1). | Arthritis and rheumatism | 33 | 15593085 |
| 1991 | Expression of a human cartilage procollagen gene (COL2A1) in mouse 3T3 cells. | The Journal of biological chemistry | 33 | 1860834 |
| 2009 | A permease encoded by STL1 is required for active glycerol uptake by Candida albicans. | Microbiology (Reading, England) | 31 | 19383674 |
| 1994 | Expression and localization of COL2A1 mRNA and type II collagen in human fetal cochlea. | Hearing research | 31 | 7806485 |
| 1984 | Localization of human type II procollagen gene (COL2A1) to chromosome 12. | Somatic cell and molecular genetics | 31 | 6594770 |
| 2019 | COL2A1 Gene Mutations: Mechanisms of Spondyloepiphyseal Dysplasia Congenita. | The application of clinical genetics | 29 | 31824186 |
| 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 |
| 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 |
| 2015 | Human articular chondrocytes with higher aldehyde dehydrogenase activity have stronger expression of COL2A1 and SOX9. | Osteoarthritis and cartilage | 26 | 26687820 |
| 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 |
| 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 |
| 2019 | The influence of probiotic diet and chondroitin sulfate administration on Ptgs2, Tgfb1 and Col2a1 expression in rat knee cartilage during monoiodoacetate-induced osteoarthritis. | Minerva medica | 24 | 30938133 |
| 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 | 23 | 35163788 |
| 2017 | A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature. | Journal of medical case reports | 23 | 28841907 |
| 2008 | Clinical evaluation and COL2A1 gene analysis in 21 Brazilian families with Stickler syndrome: identification of novel mutations, further genotype/phenotype correlation, and its implications for the diagnosis. | European journal of medical genetics | 23 | 18276201 |
| 2020 | Aom2 S: A new web-based application for DNA/RNA tandem mass spectrometry data interpretation. | Rapid communications in mass spectrometry : RCM | 22 | 32812285 |
| 2017 | Novel and recurrent COL11A1 and COL2A1 mutations in the Marshall-Stickler syndrome spectrum. | Human genome variation | 22 | 28983407 |
| 2003 | Posterior chorioretinal atrophy and vitreous phenotype in a family with Stickler syndrome from a mutation in the COL2A1 gene. | Ophthalmology | 22 | 12511349 |
| 2021 | Safflower Polysaccharide Inhibits AOM/DSS-Induced Mice Colorectal Cancer Through the Regulation of Macrophage Polarization. | Frontiers in pharmacology | 21 | 34744741 |
| 2020 | Skeletal deterioration in COL2A1-related spondyloepiphyseal dysplasia occurs prior to osteoarthritis. | Osteoarthritis and cartilage | 21 | 31958497 |
| 2016 | Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome. | Molecular vision | 21 | 27390512 |
| 2017 | Boswellia serrata resin extract alleviates azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis. | Molecular nutrition & food research | 20 | 28245338 |
| 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 |
| 2022 | Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model. | Cancer research and treatment | 19 | 35790194 |
| 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 |
| 2017 | Diverse contribution of Col2a1-expressing cells to the craniofacial skeletal cell lineages. | Orthodontics & craniofacial research | 18 | 28643905 |
| 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 |
| 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 |
| 2022 | 6- shogaol suppresses AOM/DSS-mediated colorectal adenoma through its antioxidant and anti-inflammatory effects in mice. | Journal of food biochemistry | 16 | 36125935 |
| 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 | Lactobacillus kefiranofaciens JKSP109 and Saccharomyces cerevisiae JKSP39 isolated from Tibetan kefir grain co-alleviated AOM/DSS induced inflammation and colorectal carcinogenesis. | Food & function | 15 | 35575226 |
| 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 |
| 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 |
| 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 | 13 | 8785590 |
| 2021 | Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice. | Frontiers in oncology | 12 | 34513713 |
| 2020 | A CRISPR-engineered swine model of COL2A1 deficiency recapitulates altered early skeletal developmental defects in humans. | Bone | 12 | 32450343 |
| 2020 | COL2A1 Is a Novel Biomarker of Melanoma Tumor Repopulating Cells. | Biomedicines | 12 | 32962144 |
| 2019 | Helicase-like transcription factor (Hltf) gene-deletion promotes oxidative phosphorylation (OXPHOS) in colorectal tumors of AOM/DSS-treated mice. | PloS one | 12 | 31461471 |
| 2013 | A mutation of the Col2a1 gene (G1170S) alters the transgenic murine phenotype and cartilage matrix homeostasis. | Journal of the Formosan Medical Association = Taiwan yi zhi | 12 | 24168833 |
| 2006 | Sonographic diagnosis of SEDC and double heterozygote of SEDC and achondroplasia--a report of six pregnancies. | Prenatal diagnosis | 12 | 16874841 |
| 2025 | Poria cocos polysaccharides ameliorate AOM/DSS-induced colorectal cancer in mice by remodeling intestinal microbiota composition and enhancing intestinal barrier function. | International journal of biological macromolecules | 11 | 40419041 |
No submissions yet.