Affinage

MMP13

Collagenase 3 · UniProt P45452

Length
471 aa
Mass
53.8 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MMP13 is a secreted zinc-dependent collagenase that drives extracellular matrix remodeling in skeletal development, cartilage homeostasis, tissue repair, and tumor progression, and whose own expression is governed by a dense signaling and transcriptional network (PMID:23298463, PMID:11774278). Its catalytic activity through degradation of fibrillar type I collagen and Matrigel promotes cell invasion (PMID:11774278), and remodeling of type I collagen exposes a cryptic integrin α3 ligand that activates a MMP13/ITGA3/RUNX2 osteogenic feedback loop in mesenchymal stem cells (PMID:33677160); MMP13 also directly sheds NG2 to attenuate anoikis (PMID:25166220). In bone, osteocyte-derived MMP13 is required for perilacunar/canalicular remodeling, and its loss disrupts subchondral bone and secondarily impairs cartilage, establishing MMP13-dependent bone–cartilage crosstalk (PMID:31700695); chondrocyte-specific MMP13 is in turn required for osteoarthritis progression, and its genetic or pharmacologic inhibition preserves cartilage (PMID:23298463). Transcriptionally, MMP13 is controlled through a proximal AP-1 element by a cFOS→ATF3 relay (PMID:9119388, PMID:27956552) and through RUNX2 acting at proximal and distal enhancers under control of FGF2-MEK-ERK signaling, NO/PKG1-α phosphorylation, Notch, vitamin D/VDR, and RUNX2 promoter methylation (PMID:15564063, PMID:16636074, PMID:26348136, PMID:31666602, PMID:28798419); Wnt/Lef1/β-catenin, NF-κB, and TGF-β/Smad3 inputs further activate it (PMID:17971297, PMID:16407850), while ANKRD1, p38γ, SERPINE2, and a miR-222→HDAC4 axis repress it (PMID:24515436, PMID:20633667, PMID:26305372, PMID:26673737). The proregion is essential for correct secretion: the F56S mutation causes intracellular autoactivation and autodegradation, producing spondyloepimetaphyseal dysplasia Missouri type (PMID:16167086). In neurons, MMP13 inhibition lowers BACE1 protein through a PI3K/eIF4B translational mechanism, reducing amyloid burden in an Alzheimer model (PMID:30596903).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 High

    Establishing the genomic position of MMP13 within the chromosome 11q22.3 MMP cluster placed it physically among related collagenase and stromelysin genes.

    Evidence FISH, YAC cloning, and pulsed-field gel electrophoresis mapping the CLG3 gene

    PMID:7607691

    Open questions at the time
    • Mapping alone does not define enzymatic function
    • No regulatory elements identified at this stage
  2. 1997 High

    Identifying a functional AP-1 site answered how tumor promoters and oncogenes induce MMP13, defining its core inducible transcriptional control element.

    Evidence CAT reporter transfection, EMSA, and promoter deletion in TPA-stimulated cells

    PMID:9119388

    Open questions at the time
    • Did not identify the specific AP-1 family members or temporal dynamics of binding
    • No link to upstream signaling pathways yet
  3. 2002 High

    Gain-of-function with MMP inhibitor rescue established that MMP13 enzymatic activity directly drives invasion through type I collagen and Matrigel, defining its first clear catalytic phenotype.

    Evidence Stable/adenoviral MMP13 expression in HT-1080 cells with Batimastat and TIMP-3 inhibition and invasion assays

    PMID:11774278

    Open questions at the time
    • Did not identify in vivo substrates cleaved during invasion
    • Used a single fibrosarcoma cell line
  4. 2004 High

    Linking FGF2-MEK-ERK to RUNX2 and demonstrating strain-induced ERK signaling connected mechanical and growth-factor inputs to MMP13 transcription.

    Evidence RUNX2 overexpression and promoter-reporter in chondrocytes; biaxial strain with MEK/ERK inhibitors and dominant-negative mutants in osteoblasts

    PMID:15044466 PMID:15564063

    Open questions at the time
    • RUNX2 shown not to be a direct ERK substrate, leaving the phosphorylation link indirect
    • Did not map the RUNX2 binding element on the MMP13 promoter
  5. 2006 High

    Identifying the NO/cGMP/PKG1-α axis as a RUNX2 (Cbfa-1) kinase, and Smad3 as a TGF-β effector, expanded the activating regulatory network and tied it to the OSE-2 promoter element.

    Evidence Promoter mutagenesis, kinase substrate assay, Cbfa-1 siRNA, and iNOS-KO mice; adenoviral dominant-negative Smad3/Smad7/ALK5 in SCC cells with xenografts

    PMID:16407850 PMID:16636074

    Open questions at the time
    • Cell-type-specific weighting of these inputs not resolved
    • Crosstalk between Smad3 and RUNX2 inputs not directly tested
  6. 2008 Medium

    Mass-spectrometry identification of Hsp90β and p130(cas) as AGRE-site negative regulators introduced repressive control and a route for cytokine-mediated derepression.

    Evidence MS of promoter-interacting proteins plus siRNA silencing and IL-1β treatment in chondrocytes

    PMID:18593760

    Open questions at the time
    • Direct DNA binding versus indirect complex association not fully distinguished
    • Single lab, single chondrocyte source
  7. 2009 Medium

    Defining Lef1/β-catenin and the ING2-HDAC1-mSin3A/NF-κB inputs, plus integrin-FAK-ERK-AP-1 relays from CCN family ligands, mapped Wnt and integrin signaling onto MMP13 transcription.

    Evidence ChIP/EMSA and siRNA for Lef1; reporter and complex co-expression for ING2; integrin-blocking and ChIP for Cyr61 in chondrosarcoma cells

    PMID:17971297 PMID:19126648 PMID:19437536

    Open questions at the time
    • Relative contribution of these parallel inputs in vivo unresolved
    • Several findings rest on single cell-line systems
  8. 2010 High

    Discovery that p38γ suppresses MMP13 while p38α promotes it revealed isoform-specific, opposing MAPK control, refining the cytokine signaling picture.

    Evidence Constitutively active and dominant-negative p38γ in human chondrocytes with combined p38 isoform inhibition

    PMID:20633667

    Open questions at the time
    • Downstream transcription factor mediating p38γ repression not identified
    • Mechanism of opposing isoform action unresolved
  9. 2013 High

    Chondrocyte-specific Mmp13 knockout with pharmacologic recapitulation established MMP13 as causally required for osteoarthritis cartilage degeneration, validating it as a therapeutic target.

    Evidence Tamoxifen-inducible Col2CreER;Mmp13fx/fx mice in a meniscal-ligamentous injury model plus CL82198 inhibitor with histomorphometry and TUNEL

    PMID:23298463

    Open questions at the time
    • Did not resolve which collagen substrates dominate disease progression
    • Mechanical regulation in vivo not addressed here
  10. 2013 High

    Mechanistic dissection of mechanical loading via Rac1-p38 and of ER-stress/cytokine inputs via salubrinal clarified how physical and stress signals tune MMP13 activity in cartilage.

    Evidence Knee-loading device, FRET Rac1 imaging, reciprocal Rac1 mutants, and salubrinal with NF-κB p65 siRNA in chondrocytes

    PMID:23473976 PMID:24180431

    Open questions at the time
    • How load magnitude switches between MMP13-suppressing and -inducing outcomes not fully defined
    • In vivo translation of salubrinal effect untested
  11. 2014 High

    Identification of ANKRD1, GDF5→DKK1→Wnt, and miR-222→HDAC4 as repressive nodes built out the negative-regulatory arm of MMP13 control.

    Evidence Y2H/co-IP/ChIP/EMSA with Ankrd1 KO; DKK1-inhibitor rescue with GDF5; 3'-UTR luciferase and reciprocal miR-222 manipulation with DMM mouse model

    PMID:24515436 PMID:24561281 PMID:26673737

    Open questions at the time
    • Interplay between these repressors and the activating AP-1/RUNX2 network not integrated
    • Therapeutic exploitation untested
  12. 2015 High

    Establishing NG2 shedding as an anoikis-attenuating substrate and demonstrating MMP13's role in colorectal metastasis defined direct extracellular substrate consequences for tumor cell survival and dissemination.

    Evidence MMP13 gain/loss with NG2-null controls and anoikis assays; Mmp13-KO mice and tumor-cell knockdown in a liver metastasis model with whole-organ confocal microscopy

    PMID:25166220 PMID:25880591

    Open questions at the time
    • Stromal versus tumor-derived contributions not fully partitioned mechanistically
    • NG2 cleavage site not mapped
  13. 2015 High

    Mapping distal enhancers, including a -10 kb VDR enhancer required for vitamin-D induction, revealed cis-regulatory architecture controlling basal and hormone-inducible MMP13.

    Evidence ChIP-seq, CRISPR -10 kb enhancer-deletion mice with 1,25(OH)2D3 induction, and RUNX2/OSX manipulation

    PMID:26348136

    Open questions at the time
    • Functional roles of the -20 and -30 kb enhancers in disease not resolved
    • Enhancer usage across cell types not surveyed
  14. 2016 High

    Demonstrating the cFOS→ATF3 relay at the proximal AP-1 motif explained how transient early-response signaling produces sustained MMP13 transcription.

    Evidence Temporally resolved ChIP for cFOS/ATF3, nascent transcription assay, and siRNA in stimulated chondrocytes

    PMID:27956552

    Open questions at the time
    • How ATF3 handoff is timed mechanistically not fully defined
    • Generality across non-chondrocyte cell types untested
  15. 2016 High

    Double-knockout epistasis placed MMP13 genetically downstream of HDAC4 in endochondral ossification, while ETV4 was defined as an additional direct activator in epithelial cancer.

    Evidence Hdac4/Mmp13 double-KO mice with skeletal phenotyping; ETV4 promoter-reporter and rescue with xenografts

    PMID:27320207 PMID:29996935

    Open questions at the time
    • Direct molecular link between HDAC4 and MMP13 transcription not fully delineated
    • ETV4 finding in a single epithelial system
  16. 2019 High

    Osteocyte-specific knockout established MMP13's role in perilacunar/canalicular bone remodeling and bone-cartilage crosstalk, while lung and vascular studies revealed antifibrotic and SMC-migratory roles in other tissues.

    Evidence DMP1-Cre;Mmp13fl/fl osteocyte knockout; Mmp13-null bleomycin lung fibrosis model; IL-17A/TRAF3IP2 signaling in aortic SMCs

    PMID:30785343 PMID:31074012 PMID:31700695

    Open questions at the time
    • Substrate basis of antifibrotic versus profibrotic outcomes unresolved
    • Tissue-specific regulatory differences not integrated
  17. 2019 High

    Discovery of a PI3K/eIF4B translational mechanism linking MMP13 inhibition to reduced BACE1 protein extended MMP13 biology into a novel CNS, non-catalytic-output pathway with Alzheimer relevance.

    Evidence Small-molecule screen, eIF4B S422R and BACE1 5'UTR mutagenesis, and hippocampal Mmp13 knockdown in APPswe/PS1E9 mice with behavioral testing

    PMID:30596903

    Open questions at the time
    • How extracellular MMP13 activity couples to intracellular eIF4B phosphorylation is mechanistically incomplete
    • Direct MMP13 substrate in this pathway not identified
  18. 2021 Medium

    Defining the MMP13/ITGA3/RUNX2 cryptic-ligand feedback loop showed how MMP13-mediated collagen remodeling actively instructs osteogenic differentiation rather than merely degrading matrix.

    Evidence Recombinant MMP13 collagen pre-treatment, MMP13 knockdown in hMSCs, RUNX2 promoter ChIP, and in vivo implants

    PMID:33677160

    Open questions at the time
    • Identity of the cryptic integrin α3 ligand epitope not defined
    • Single-lab in vivo validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the activating (AP-1/RUNX2/Wnt/Smad/NF-κB) and repressive (ANKRD1/p38γ/SERPINE2/miR-222-HDAC4) networks are integrated quantitatively to set MMP13 output in a given tissue, and how extracellular catalytic activity connects to intracellular translational effects, remains unresolved.
  • No unified model of competing transcriptional inputs
  • Mechanistic coupling between secreted MMP13 and intracellular eIF4B/BACE1 regulation unknown
  • Tissue-specific substrate repertoire incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
COL1A1ITGA3NG2RUNX2

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The MMP13 gene promoter contains a functional AP-1 site that confers responsiveness to tumor promoters (TPA) and oncogene products; transient transfection with CAT reporter constructs demonstrated that the AP-1 site is responsible for TPA-inducibility, and DNA binding assays showed specific complex formation between nuclear proteins and the AP-1-containing promoter sequences. Unlike other MMP gene promoters, no significant synergistic effect was found between AP-1 and PEA-3 elements in MMP13. Transient transfection with CAT reporter constructs, DNA binding/EMSA with nuclear extracts, promoter deletion analysis Genomics High 9119388
1995 The human MMP13 (CLG3) gene is physically mapped to chromosome 11q22.3 and is tightly clustered with other MMP genes (MMP1/CLG1, MMP3/STMY1, MMP2/STMY2), with CLG3 located on the telomeric side of the cluster. Fluorescence in situ hybridization (FISH), YAC cloning, pulsed-field gel electrophoresis Genomics High 7607691
2005 A missense mutation F56S in the proregion domain of MMP13 causes spondyloepimetaphyseal dysplasia Missouri type (SEMD[MO]). Structural modeling predicted the F56S substitution creates a hydrophobic cavity causing misfolding, autoactivation, and intracellular autodegradation. Expression of F56S MMP13 in HEK cells confirmed abnormal intracellular autoactivation and autodegradation, with only enzymatically inactive small fragments secreted — establishing that MMP13 proregion integrity is required for normal secretion and extracellular enzymatic activity. Genome-wide linkage analysis, DNA sequencing, structural modeling, expression of wild-type vs. mutant MMP13 in HEK cells with functional enzymatic assays The Journal of clinical investigation High 16167086
2004 RUNX2 overexpression in articular chondrocytes increases responsiveness to FGF2, leading to elevated MMP-13 promoter activity and enzyme accumulation. FGF2 activates RUNX2 via the MEK/ERK pathway (MEK/ERK inhibitors block FGF2- and RUNX2-driven MMP-13 upregulation and RUNX2 phosphorylation), but RUNX2 is unlikely to be a direct ERK1/2 substrate. RUNX2 overexpression in articular chondrocytes, MMP-13 promoter-reporter assay, MEK/ERK inhibitor treatment, RUNX2 phosphorylation assay, immunohistochemistry in OA cartilage Osteoarthritis and cartilage High 15564063
2004 Mechanical (biaxial) strain induces MMP-13 expression in MC3T3-E1 osteoblastic cells through the MEK-ERK signaling pathway. ERK pathway inhibitor PD98059 and dominant-negative MEK1/2 (MEK K97R) and ERK2 mutants blocked strain-induced MMP-13 and c-fos mRNA expression; the induction does not require de novo protein synthesis. Biaxial strain device, Western blotting, RT-PCR, zymography, MEK/ERK inhibitors, dominant-negative mutant transfection The Journal of biological chemistry High 15044466
2006 Nitric oxide (NO) and cGMP regulate MMP-13 expression in MC3T3-E1 osteoblasts during differentiation via activation of PKG1-α, which phosphorylates Cbfa-1 (RUNX2) and promotes its nuclear translocation. MMP-13 promoter activation by NO/8-Br-cGMP/PKG1-α is partially dependent on the OSE-2 (Cbfa-1 binding) element; Cbfa-1 siRNA knockdown blocks MMP-13 expression without affecting endogenous NO production; iNOS-deficient mice show reduced MMP-13 and Cbfa-1 in vivo. MMP-13 promoter-reporter assay with OSE-2 mutation, PKG1-α dominant-positive transfection, Cbfa-1 siRNA silencing, Cbfa-1 phosphorylation in vitro by PKG, iNOS-KO mouse immunohistology Journal of cell science High 16636074
2002 Wild-type p53 delivered adenovirally potently suppresses MMP-13 (and MMP-1) production in head and neck SCC cells with mutant p53 (71–92% reduction), and reduces Matrigel invasion by 35%, independently of p53's pro-apoptotic effect. MMP-2 and MMP-9 production were not altered, indicating specificity of p53-mediated suppression for MMP-13 and MMP-1. Adenoviral p53 gene delivery, ELISA for proMMP-13 and MMP-1, Matrigel invasion assay, Western blotting for p21Waf1/Cip1 Oncogene Medium 11850838
2002 Constitutive expression of MMP-13 in HT-1080 fibrosarcoma cells markedly increases invasion through type I collagen and Matrigel, an effect blocked by the broad MMP inhibitor Batimastat (BB-94) and TIMP-3, establishing MMP-13 as a potent invasion-promoting collagenase acting through its enzymatic activity. Stable transfection and adenoviral transduction of MMP-13 expression vector in HT-1080 cells, Matrigel and type I collagen invasion assays, MMP inhibitor treatment International journal of cancer High 11774278
2006 Smad3 signaling downstream of TGF-β upregulates MMP-13 expression and invasion in head and neck SCC cells. Adenoviral delivery of dominant-negative Smad3, Smad7, or kinase-dead ALK5 potently suppressed basal and TGF-β-induced MMP-13 and MMP-1 expression and inhibited invasion; Smad3 overexpression augmented TGF-β-driven MMP-13 upregulation. Basal p38 activation in these cells was also Smad-dependent. Adenoviral delivery of Smad7, dominant-negative Smad3, kinase-defective ALK5, and Smad3 overexpression; MMP-13/MMP-1 ELISA; Matrigel/collagen invasion assay; in vivo SCID xenograft model Oncogene High 16407850
2007 Lef1 and β-catenin (Wnt/β-catenin signaling) synergistically upregulate MMP13 transcription in chondrocytes. A Lef1 binding site was mapped to the 3' region of the MMP13 genomic locus; Lef1/β-catenin binding was confirmed by ChIP and EMSA; Lef1 siRNA knockdown suppresses IL-1β-mediated MMP13 induction; Lef1/β-catenin transactivates MMP13 promoter activity. ChIP assay, EMSA, Lef1 siRNA knockdown, MMP13 promoter-reporter assay, co-transfection of Lef1 and β-catenin Biochemical and biophysical research communications High 17971297
2008 Hsp90β and p130(cas), identified by mass spectrometry as proteins interacting with the AGRE site of the MMP-13 promoter in L-OA chondrocytes, act as negative regulators of MMP-13 expression. siRNA silencing of p130(cas) increases MMP-13 expression ~4-fold and Hsp90β silencing ~2-fold; combined silencing has an additive effect. IL-1β decreases p130(cas) and Hsp90β expression, providing a mechanism for cytokine-mediated MMP-13 upregulation. Mass spectrometry identification of promoter-interacting proteins, siRNA silencing, real-time PCR, ELISA, Western blotting Annals of the rheumatic diseases Medium 18593760
2009 Cyr61 increases MMP-13 expression and migration in chondrosarcoma cells via αvβ3 integrin → FAK → ERK → AP-1 (c-Fos/c-Jun) signaling. RGD peptide, αvβ3 antibody, MEK inhibitors, and AP-1 decoy oligonucleotides each block Cyr61-induced MMP-13 upregulation; ChIP demonstrates increased binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter. Cell migration assay, siRNA/inhibitor pharmacology, FAK/ERK phosphorylation assays, AP-1 decoy ODN, ChIP on MMP-13 promoter AP-1 site Carcinogenesis Medium 19126648
2009 ING2 upregulation in colon cancer increases MMP13 expression and cancer cell invasion. ING2 regulates MMP13 through an ING2-HDAC1-mSin3A complex; co-expression of ING2 with HDAC1 or mSin3A further induces MMP13, confirmed by both ING2 overexpression and knockdown experiments. NF-κB binds the ING2 promoter as shown by EMSA and luciferase assay. Microarray, ING2 overexpression and knockdown, MMP13 reporter assay, EMSA/luciferase for NF-κB binding, in vitro Matrigel invasion assay International journal of cancer Medium 19437536
2010 p38γ isoform is activated by IL-1β and fibronectin fragments in human articular chondrocytes and counter-intuitively suppresses MMP-13 production. Constitutively active p38γ decreased MMP-13 production while dominant-negative p38γ increased it. Combined inhibition of p38α+p38γ resulted in less MMP-13 suppression than inhibiting p38α alone, confirming the opposing roles of these isoforms. Antibody array and immunoblotting for p38 isoform phosphorylation, constitutively active and dominant-negative p38γ transfection/transduction, RT-PCR, ELISA, immunoblotting for MMP-13 Osteoarthritis and cartilage High 20633667
2011 CCN3 increases MMP-13 expression and migration in chondrosarcoma cells via αvβ3/αvβ5 integrin → FAK → PI3K → Akt → NF-κB (p65) signaling. αvβ3/αvβ5 antibodies, PI3K inhibitors, Akt inhibitors, and NF-κB inhibitors each block CCN3-induced MMP-13 upregulation; ChIP demonstrates p65 binding to the NF-κB element on the MMP-13 promoter. Cell migration assay, pharmacologic inhibitors, FAK/PI3K/Akt phosphorylation assays, NF-κB luciferase reporter, ChIP on MMP-13 NF-κB site Journal of cellular physiology Medium 21344378
2011 CCN2 C-terminal (CT) module directly binds FGF2 (Kd = 5.5 nM by surface plasmon resonance) and, when combined with FGF2, nullifies FGF2-driven MMP-13 (and MMP-9) production by chondrocytes by reducing ERK1/2, p38 MAPK, and JNK phosphorylation. CCN2 (full-length) binds FGF receptor 1 (Kd = 362 nM), but the CT module alone does not, indicating CCN2 modulates FGF2/MMP-13 signaling through a distinct interaction. Solid-phase binding assay, co-immunoprecipitation–Western blot, surface plasmon resonance (SPR), MMP-9 and MMP-13 activity measurement, ERK/p38/JNK phosphorylation Western blot Endocrinology High 21914781
2012 MMP-13 promotes tumor angiogenesis directly and indirectly: conditioned medium from MMP-13-overexpressing cells and recombinant MMP-13 protein both promote capillary tube formation in vitro and in vivo; this effect is mediated through FAK and ERK activation. MMP-13 also promotes secretion of VEGF-A from fibroblasts and endothelial cells. MMP-13 overexpression/conditioned medium assay, recombinant MMP-13 treatment, capillary tube formation assay in vitro and in vivo, FAK/ERK phosphorylation assays, VEGF-A secretion measurement The Journal of biological chemistry Medium 22992737
2012 Endothelin-1 (ET-1) increases MMP-13 expression and migration in chondrosarcoma cells via FAK → PI3K → Akt → mTOR → IKKα/β → NF-κB signaling. Inhibitors of each kinase step and NF-κB reduce ET-1-induced MMP-13 and migration; ET-1 induces sequential phosphorylation of FAK, PI3K, Akt, and mTOR, and NF-κB luciferase activity. Cell migration assay, pharmacologic inhibitors of FAK/PI3K/Akt/mTOR/NF-κB, NF-κB luciferase reporter, FAK/Akt/mTOR phosphorylation Western blot, MMP-13 ELISA Journal of cellular physiology Medium 21959927
2013 MMP13 is required for OA progression in cartilage: conditional chondrocyte-specific knockout of Mmp13 (Mmp13Col2ER mice) decelerates cartilage degeneration after meniscal-ligamentous injury, preserving type II collagen, proteoglycan levels, and reducing chondrocyte apoptosis. The MMP13 inhibitor CL82198 (confirmed to inhibit MMP13 activity in vitro by >85%) recapitulates this protective effect in vivo. Conditional knockout mouse (tamoxifen-inducible Col2CreER;Mmp13fx/fx), OA induction by MLI surgery, histomorphometry, IHC, TUNEL staining, in vitro MMP13 activity ELISA Arthritis research & therapy High 23298463
2013 Knee loading reduces MMP13 activity in mouse cartilage through Rac1 GTPase-mediated p38 MAPK signaling. Silencing Rac1 reduces MMP13 expression and p-p38; constitutively active Rac1 increases MMP13 activity while dominant-negative Rac1 decreases it; shear-induced MMP13 reduction is associated with decreased p-p38 and p-NFκB, with Rac1 acting upstream of p38. Knee loading device in OA mouse model, primary chondrocyte shear assay, FRET live imaging of Rac1 activity, siRNA Rac1 knockdown, constitutively active and dominant-negative Rac1 transfection, MMP13 activity assay BMC musculoskeletal disorders High 24180431
2013 Salubrinal suppresses MMP13 expression and activity in chondrocytes through p38 MAPK and NFκB signaling. NFκB p65 siRNA silencing reduces inflammatory cytokine-driven MMP13 activity. Tunicamycin (ER stress) activates p38 MAPK while TNFα/IL-1β activate both p38 and NFκB; salubrinal reduces MMP13 in both conditions. siRNA knockdown of NFκB p65, p38 MAPK and NFκB phosphorylation assays, salubrinal treatment, MMP13 activity assay, RT-PCR and Western blot Osteoarthritis and cartilage Medium 23473976
2014 ANKRD1 acts as a transcriptional repressor of MMP13 via the AP-1 site. ANKRD1 associates with nucleolin (yeast two-hybrid, co-IP); deletion of Ankrd1 enhances basal and PMA-induced MMP13 promoter activity; Ankrd1 overexpression decreases MMP13; ChIP shows greater c-Jun binding to the AP-1 site in KO vs. FLOX fibroblasts; EMSA patterns suggest additional AP-1 binding factors in the absence of Ankrd1. Yeast two-hybrid, co-immunoprecipitation, MMP13 promoter-reporter assay, Ankrd1 KO and overexpression, ChIP for c-Jun at MMP13 AP-1 site, EMSA Molecular and cellular biology High 24515436
2014 GDF5 inhibits MMP13 expression in human chondrocytes via upregulation of canonical Wnt inhibitor DKK1. GDF5 stimulation increases DKK1 and FRZB expression, inhibits β-catenin-driven Wnt signaling, and reduces MMP13 protein levels; blocking DKK1 (with WAY-262611) prevents GDF5-mediated MMP13 suppression, establishing the GDF5→DKK1→Wnt inhibition→MMP13 axis. qPCR, ELISA for MMP13/DKK1/β-catenin, Wnt3a and CHIR-99021 stimulation, DKK1 inhibitor (WAY-262611) rescue experiment, human chondrocyte pellet culture Osteoarthritis and cartilage Medium 24561281
2014 miR-222 directly targets HDAC-4 (confirmed by 3'-UTR luciferase reporter assay); miR-222 overexpression in chondrocytes suppresses HDAC-4 and subsequently MMP-13, reducing apoptosis. HDAC inhibitor TSA also suppresses MMP-13, while HDAC-4 overexpression increases MMP-13, placing HDAC-4 upstream of MMP-13 in a miR-222 → HDAC-4 → MMP-13 pathway. 3'-UTR luciferase reporter assay, miR-222 precursor/inhibitor delivery, HDAC-4 overexpression, TSA treatment, Western blotting, in vivo DMM mouse model with intra-articular injection BBA clinical High 26673737
2015 MMP-13 directly cleaves and sheds NG2 from the cell surface, attenuating anoikis. MMP-13 expression increases during late anoikis conditions; MMP-13 inhibitor or siRNA knockdown increased anoikis by blocking NG2 release; exogenous MMP-13 or overexpression reduced anoikis by more effectively shedding NG2; MMP-13 inhibition had no effect on anoikis in NG2-null cells, confirming NG2 as the relevant substrate. MMP-13 siRNA knockdown, MMP-13 inhibitor treatment, MMP-13 overexpression, exogenous recombinant MMP-13, anoikis assay, NG2-null cell controls, conditioned medium analysis DNA and cell biology Medium 25166220
2015 SENP2 inhibits MMP13 expression in bladder cancer cells via de-SUMOylation of TBL1/TBLR1, which prevents formation of TBL1/TBLR1–β-catenin complexes and nuclear translocation of β-catenin that would otherwise activate MMP13 transcription. WNT ligands induce TBL1/TBLR1 SUMOylation to facilitate β-catenin nuclear entry and MMP13 activation. siRNA knockdown, β-catenin nuclear fractionation, SUMOylation assay for TBL1/TBLR1, MMP13 promoter reporter, Western blot Scientific reports Medium 26369384
2015 Stromal and tumor-derived MMP13 both contribute to colorectal cancer extravasation and liver metastasis establishment. Mmp13-deficient mice show reduced tumor extravasation from hepatic vasculature (whole-organ confocal microscopy); MMP13 knockdown in tumor cells decreases migratory and invasive properties in vitro and metastatic burden in vivo. Mmp13 knockout mice, splenic injection liver metastasis model, whole-organ confocal microscopy for extravasation, MMP13 stable knockdown cell lines, MTT/migration/invasion assays Molecular cancer High 25880591
2015 SERPINE2 inhibits IL-1α-induced MMP-13 expression in human chondrocytes through suppression of ERK1/2, NF-κB, and AP-1 pathways. Recombinant SERPINE2 reduces IL-1α-stimulated MMP-13 production, and the inhibitory effect is mediated through these three signaling cascades. siRNA/recombinant SERPINE2 treatment, ERK1/2 and NF-κB and AP-1 Western blotting, RT-qPCR for MMP-13 in primary chondrocytes and T/C-28a2 cells PloS one Medium 26305372
2015 TAK1 (MEKK7) acts as a downstream mediator of IL-1β signaling that regulates MMP-13 expression; TAK1 siRNA silencing in SW1353 chondrosarcoma cells reduces IL-1β-induced MMP-13 release by 40–50% and TNF-α by 60–70%. TAK1 siRNA knockdown, IL-1β stimulation, MMP-13 and TNF-α quantification by ELISA, qRT-PCR Biomedicine & pharmacotherapy Medium 16459052
2016 ATF3 directly binds the proximal AP-1 motif on the MMP13 promoter in stimulated chondrocytes at time points when cFOS is no longer bound, and is required for sustained MMP13 expression. ATF3 expression is AP-1 (cFOS/cJUN)-dependent. siRNA silencing of ATF3 is as selective for MMP13 suppression as cFOS silencing. Protein synthesis inhibition after early FOS expression reduces MMP13 expression, consistent with an intermediate regulatory factor requirement. ChIP assay for cFOS and ATF3 binding to MMP13 promoter, nascent hnRNA transcription assay, siRNA silencing (ATF3, cFOS, cJUN), protein synthesis inhibitor, mRNA transcriptome analysis The Journal of biological chemistry High 27956552
2016 ETV4 transcription factor directly regulates MMP13 promoter activity in mammary epithelial cells; MMP13 functions downstream of ETV4 to promote proliferation, migration, invasion, and anchorage-independent growth; MMP13 inhibition partially rescues ETV4-driven phenotypes and reduces tumor formation in immunodeficient mice. MMP13 promoter-reporter constructs with ETV4 activation, MMP13 overexpression/knockdown, cell proliferation/migration/invasion assays, in vivo xenograft assay Breast cancer research : BCR Medium 29996935
2016 High molecular weight hyaluronic acid (HA) inhibits TNF-α-induced MMP13 expression in chondrocytes through HA-CD44 interaction, which induces DUSP10/MKP5 (a negative regulator of p38 MAPK and JNK), thereby suppressing p38 and JNK phosphorylation and AP-1 transcriptional activity. CD44 function-blocking antibody abrogates HA-mediated MMP13 inhibition. CD44 function-blocking mAb, p38/JNK phosphorylation Western blot, AP-1 luciferase reporter, DUSP10/MKP5 expression by RT-PCR/Western blot/immunofluorescence, ELISA for MMP13 Journal of orthopaedic research Medium 27101204
2016 HDAC7 promotes MMP-13 gene expression in OA chondrocytes; HDAC7 siRNA knockdown in SW1353 cells strongly suppresses both IL-1-dependent and -independent MMP-13 gene expression. HDAC7 siRNA knockdown, IL-1 stimulation, real-time PCR for MMP-13, immunohistochemistry of OA cartilage Modern rheumatology Medium 19784544
2016 MMP-13 is one of the critical downstream mediators of HDAC4's effect on the skeleton. Hdac4/Mmp13 double-knockout mice are significantly larger, survive longer, and have partially recovered growth plate zones compared to Hdac4-/- mice alone, establishing genetic epistasis where HDAC4 acts upstream of MMP-13 to regulate endochondral ossification and bone remodeling. Hdac4/Mmp13 double-knockout mouse generation, body size measurement, histology (Safranin O, ALP, TRAP), micro-CT analysis of tibiae Bone High 27320207
2015 Distal enhancers at –10, –20, and –30 kb upstream of Mmp13 transcriptional start site regulate its basal and hormone-inducible expression. The –10 kb enhancer binds VDR and is specifically required for 1,25(OH)2D3-induced Mmp13 upregulation (demonstrated by CRISPR deletion in mice that fail to upregulate Mmp13 in response to vitamin D despite normal bone density). PTH and OSX act through the –30 kb RUNX2-bound enhancer and promoter-proximal regions, not through the –10 kb element. ChIP-seq, CRISPR-deleted –10 kb enhancer mouse model, in vivo 1,25(OH)2D3 induction assay, RUNX2 deletion and OSX overexpression in cells, promoter-reporter assays The Journal of steroid biochemistry and molecular biology High 26348136
2017 DNA methylation of the RUNX2 P1 promoter inversely correlates with RUNX2 mRNA levels in OA chondrocytes; methylation treatment of the RUNX2 promoter in vitro decreases its activity. RUNX2 overexpression enhances MMP13 promoter activity independently of MMP13 promoter methylation status, establishing RUNX2 availability (controlled by RUNX2 P1 methylation) as a determinant of MMP13 transcription in OA. Bisulfite sequencing for CpG methylation, RUNX2 promoter-reporter with methylation treatment, RUNX2 overexpression in chondrocytes, MMP13 promoter-reporter assay Scientific reports Medium 28798419
2017 PKR activation triggers TNF-α-induced PKC phosphorylation, leading to NADPH oxidase-mediated oxidative stress, ERK/NF-κB-driven inflammation (COX-2, IL-8), and MMP-13 upregulation in chondrocytes. Activated ERK pathway also impedes PPAR-γ-mediated inhibition of MMP-13. Poly(I:C)-mediated PKR activation reproduces the MMP-13 induction. PKR activation with poly(I:C) and TNF-α, PKC phosphorylation assays, NADPH oxidase activity, ERK/NF-κB signaling assays, MMP-13 expression by Western blot/RT-PCR Redox biology Medium 28869834
2017 Notch signaling regulates MMP-13 expression in chondrocytes through Runx2. Jagged-1-mediated Notch activation increases MMP-13 and Runx2 expression; DAPT-mediated Notch inhibition reduces them. Runx2 RNAi significantly attenuates the sensitivity of MMP-13 expression to Notch modulation both in vitro and in vivo (intra-articular shRunx2 lentivirus in rats), establishing Runx2 as a downstream mediator of Notch-driven MMP-13 regulation. Jagged-1/DAPT treatment, shRunx2 lentiviral knockdown (in vitro and in vivo intra-articular injection), ChIP for Notch signaling markers, CCK-8, EdU, immunohistochemistry Scientific reports Medium 31666602
2019 Osteocyte-derived MMP13 is required for perilacunar/canalicular remodeling (PLR) of subchondral bone. Osteocyte-specific Mmp13 ablation (using 9.6-kb DMP1-Cre) suppresses PLR, compromises cartilage proteoglycan content, collagen II, aggrecan, chondrocyte MMP13, and increases cartilage lesions—establishing MMP13-dependent bone-cartilage crosstalk. Osteocyte-specific conditional knockout (DMP1-Cre;Mmp13fl/fl), histology, IHC for PLR markers, confocal microscopy of canalicular networks, μCT Bone research High 31700695
2019 MMP13 inhibition reduces BACE1 protein levels in neurons through a PI3K/eIF4B (S422) translational regulation mechanism, independently of BACE1 transcription or protein degradation. The eIF4B S422 site and BACE1 5'UTR are required for this effect. In APPswe/PS1E9 Alzheimer mice, hippocampal Mmp13 knockdown or systemic CL82198 reduces BACE1, amyloid-β load, and improves cognition. High-throughput small molecule screen, CL82198 MMP13 inhibitor, eIF4B S422R mutation, BACE1 5'UTR deletion, Mmp13 hippocampal knockdown by AAV in AD mice, BACE1 protein assays, behavioral memory tests Brain : a journal of neurology High 30596903
2019 Bleomycin-induced lung fibrosis is delayed in resolution in Mmp13-null mice, with decreased overall collagenolytic activity and persistent fibrotic foci. MMP13 is expressed mainly by alveolar and interstitial macrophages during inflammation and fibrosis resolution, playing an antifibrotic role in lung repair. Mmp13-null mice, bleomycin intratracheal lung injury model, BAL cytokine array, gelatinase activity assay, histology, immunostaining for cell types American journal of physiology. Lung cellular and molecular physiology High 30785343
2019 IL-17A promotes MMP-13 expression and activation in human aortic smooth muscle cells through TRAF3IP2-dependent signaling (JNK, p38 MAPK, AP-1, NF-κB, CREB activation). RECK overexpression attenuates MMP-13 activity (without affecting its mRNA or protein levels), inhibiting SMC migration. Recombinant MMP-13 stimulates SMC migration in part via ERK activation. TRAF3IP2 siRNA knockdown, RECK overexpression, recombinant MMP-13 treatment, MMP-13 activity assay, SMC migration assay, JNK/p38/AP-1/NF-κB activation assays Journal of cellular physiology Medium 31074012
2018 PKD3 (PRKD3) is required for IL-1- and OSM-induced MMP13 expression in human chondrocytes. PKD phosphorylation is driven by atypical PKCι; PKD3-specific siRNA silencing reduces MMP13/MMP1 expression. PKD3 depletion reduces STAT3 serine phosphorylation and phosphorylation of all three MAPK groups, and lowers expression of AP-1 genes FOS and JUN as well as ATF3, which collectively drive MMP13 expression. PKD isoform-specific siRNA silencing, pan-PKD inhibitor, STAT3 and MAPK phosphorylation Western blot, FOS/JUN/ATF3 qPCR, MMP13 expression assays PloS one Medium 29652915
2021 MMP13 remodels type I collagen matrix to expose a cryptic integrin α3 ligand, stimulating osteogenic differentiation of human MSCs via a MMP13/integrin α3 (ITGA3)/RUNX2 positive feedback loop. RUNX2 transcription factor binds the MMP13 promoter. Recombinant MMP13 pre-treatment of collagen matrix increases osteogenic differentiation and in vivo bone formation; MMP13 knockdown in hMSCs on collagen matrix reduces differentiation. MMP13 knockdown (siRNA), recombinant MMP13 collagen pre-treatment, RUNX2 promoter ChIP, integrin α3 and FAK signaling assays, in vivo subcutaneous implant in nude mice Acta biomaterialia Medium 33677160
2017 ATP6V1H loss activates MMP13 (and MMP9) expression in zebrafish bone; small molecule inhibition of MMP9/MMP13 significantly restores bone mass in atp6v1h mutants, placing MMP13 downstream of ATP6V1H-mediated V-ATPase activity in a bone development pathway. CRISPR/Cas9 knockout of atp6v1h in zebrafish, MMP inhibitor treatment, bone mass measurement, mmp13 expression analysis PLoS genetics Medium 28158191
2008 Ultrasound stimulation increases MMP-13 expression in osteoblasts through p38 and JNK signaling pathways. p38 inhibitor (SB203580) or JNK inhibitor (SP600125), but not ERK inhibitor (PD98059), attenuate US-induced MMP-13; dominant-negative p38 or JNK mutants confirm this. US stimulation enhances c-Fos/c-Jun binding to the AP-1 element on the MMP-13 promoter and increases AP-1 luciferase activity. Ultrasound stimulation device, pharmacologic p38/JNK/ERK inhibitors, dominant-negative p38/JNK transfection, AP-1 luciferase reporter, ChIP/AP-1 element binding assay, RT-PCR, zymography Journal of cellular physiology Medium 17941091
2009 In the mouse p53+/- osteosarcoma model, the MMP13 gene is co-amplified on chromosome 9A1 (syntenic with human 11q22), and MMP13 shRNA knockdown reduces osteosarcoma tumor growth in immunodeficient mice, establishing that elevated MMP13 expression enhances osteosarcoma cell survival. Array CGH, lentiviral shRNA knockdown, transplantation into immunodeficient mice, tumor growth measurement Cancer research Medium 19276372

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis research & therapy 417 23298463
2016 Circular RNA Related to the Chondrocyte ECM Regulates MMP13 Expression by Functioning as a MiR-136 'Sponge' in Human Cartilage Degradation. Scientific reports 252 26931159
2004 Regulation of MMP-13 expression by RUNX2 and FGF2 in osteoarthritic cartilage. Osteoarthritis and cartilage 244 15564063
2017 New insights on the MMP-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis research & therapy 239 29126436
2022 The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. International journal of molecular sciences 234 35163727
2008 Joint diseases and matrix metalloproteinases: a role for MMP-13. Current pharmaceutical biotechnology 230 18289056
1997 Structural analysis and promoter characterization of the human collagenase-3 gene (MMP13). Genomics 169 9119388
2012 Matrix metalloproteinase-13 (MMP-13) directly and indirectly promotes tumor angiogenesis. The Journal of biological chemistry 114 22992737
2000 Differential expression of MT1-MMP (MMP-14) and collagenase III (MMP-13) genes in normal and wounded rat corneas. Investigative ophthalmology & visual science 102 10967042
2019 Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis. Bone research 95 31700695
2014 MicroRNA-222 regulates MMP-13 via targeting HDAC-4 during osteoarthritis pathogenesis. BBA clinical 85 26673737
2009 MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer research 84 19276372
2005 MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO). The Journal of clinical investigation 84 16167086
2004 Mechanical strain induces collagenase-3 (MMP-13) expression in MC3T3-E1 osteoblastic cells. The Journal of biological chemistry 84 15044466
2003 Expression of MMP-8 and MMP-13 genes in the periodontal ligament during tooth movement in rats. Journal of dental research 81 12885852
2006 Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells. Oncogene 79 16407850
1999 Expression and regulation of collagenase-3 (MMP-13) in human malignant tumors. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 79 10190279
2014 GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition. Osteoarthritis and cartilage 78 24561281
2017 Effect of inhibiting MMP13 and ADAMTS5 by intra-articular injection of small interfering RNA in a surgically induced osteoarthritis model of mice. Cell and tissue research 77 28120109
2011 Effects and relationship of ERK1 and ERK2 in interleukin-1β-induced alterations in MMP3, MMP13, type II collagen and aggrecan expression in human chondrocytes. International journal of molecular medicine 76 21305249
2012 Endothelin-1 promotes MMP-13 production and migration in human chondrosarcoma cells through FAK/PI3K/Akt/mTOR pathways. Journal of cellular physiology 73 21959927
2016 PAI-1, a target gene of miR-143, regulates invasion and metastasis by upregulating MMP-13 expression of human osteosarcoma. Cancer medicine 72 26817521
2020 MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis. Journal of nanobiotechnology 68 32854712
2009 Cyr61 increases migration and MMP-13 expression via alphavbeta3 integrin, FAK, ERK and AP-1-dependent pathway in human chondrosarcoma cells. Carcinogenesis 67 19126648
2009 Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis. Modern rheumatology 66 19784544
2019 Circ_0136474 and MMP-13 suppressed cell proliferation by competitive binding to miR-127-5p in osteoarthritis. Journal of cellular and molecular medicine 65 31402547
2016 Cytokine-induced MMP13 Expression in Human Chondrocytes Is Dependent on Activating Transcription Factor 3 (ATF3) Regulation. The Journal of biological chemistry 61 27956552
2004 Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness. BMC cancer 60 15291964
2002 Adenoviral delivery of p53 gene suppresses expression of collagenase-3 (MMP-13) in squamous carcinoma cells. Oncogene 60 11850838
2005 Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: a major induction of stromal MMP-13. International journal of cancer 58 15551360
2020 FTO promotes cell proliferation and migration in esophageal squamous cell carcinoma through up-regulation of MMP13. Experimental cell research 56 32035950
2018 ETV4 transcription factor and MMP13 metalloprotease are interplaying actors of breast tumorigenesis. Breast cancer research : BCR 56 29996935
2015 Clusterin facilitates metastasis by EIF3I/Akt/MMP13 signaling in hepatocellular carcinoma. Oncotarget 56 25609201
2020 Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway. International journal of molecular sciences 54 33287358
2020 Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis. Cell death and differentiation 53 32042099
2017 PKR activation causes inflammation and MMP-13 secretion in human degenerated articular chondrocytes. Redox biology 51 28869834
1995 The human collagenase-3 (CLG3) gene is located on chromosome 11q22.3 clustered to other members of the matrix metalloproteinase gene family. Genomics 51 7607691
2020 Melatonin impedes prostate cancer metastasis by suppressing MMP-13 expression. Journal of cellular physiology 50 33251599
2002 Reduction of cytokine-induced expression and activity of MMP-1 and MMP-13 by mechanical strain in MH7A rheumatoid synovial cells. Matrix biology : journal of the International Society for Matrix Biology 50 12009332
2020 Long non-coding RNA LINC00511/miR-150/MMP13 axis promotes breast cancer proliferation, migration and invasion. Biochimica et biophysica acta. Molecular basis of disease 49 33031905
2017 DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes. Scientific reports 49 28798419
2015 SERPINE2 Inhibits IL-1α-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-κB/AP-1 Pathways. PloS one 49 26305372
2017 ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13. PLoS genetics 48 28158191
2019 MMP13 inhibition rescues cognitive decline in Alzheimer transgenic mice via BACE1 regulation. Brain : a journal of neurology 47 30596903
2015 Host and tumor derived MMP13 regulate extravasation and establishment of colorectal metastases in the liver. Molecular cancer 45 25880591
2006 Cbfa-1 mediates nitric oxide regulation of MMP-13 in osteoblasts. Journal of cell science 45 16636074
2011 Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes. Endocrinology 44 21914781
2005 TAK1 downregulation reduces IL-1beta induced expression of MMP13, MMP1 and TNF-alpha. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 43 16459052
2006 Increase of MMP-13 expression in multi-stage oral carcinogenesis and epigallocatechin-3-gallate suppress MMP-13 expression. Oral diseases 42 16390465
2016 CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer. Oncotarget 41 27356745
2014 The MUC1 oncomucin regulates pancreatic cancer cell biological properties and chemoresistance. Implication of p42-44 MAPK, Akt, Bcl-2 and MMP13 pathways. Biochemical and biophysical research communications 41 25511698
2011 CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway. Journal of cellular physiology 41 21344378
2002 Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT-1080 cells. International journal of cancer 40 11774278
2024 MMP13-targeted siRNA-loaded micelles for diagnosis and treatment of posttraumatic osteoarthritis. Bioactive materials 39 38689658
2019 Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3). American journal of physiology. Lung cellular and molecular physiology 39 30785343
2019 Notch Signaling Regulates MMP-13 Expression via Runx2 in Chondrocytes. Scientific reports 39 31666602
2009 ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. International journal of cancer 39 19437536
2019 IL-1β Damages Fibrocartilage and Upregulates MMP-13 Expression in Fibrochondrocytes in the Condyle of the Temporomandibular Joint. International journal of molecular sciences 37 31067826
2014 ANKRD1 acts as a transcriptional repressor of MMP13 via the AP-1 site. Molecular and cellular biology 37 24515436
2013 Salubrinal reduces expression and activity of MMP13 in chondrocytes. Osteoarthritis and cartilage 37 23473976
2021 Cryptic ligand on collagen matrix unveiled by MMP13 accelerates bone tissue regeneration via MMP13/Integrin α3/RUNX2 feedback loop. Acta biomaterialia 36 33677160
2019 Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population. Biomolecules 35 30889876
2016 AJUBA promotes the migration and invasion of esophageal squamous cell carcinoma cells through upregulation of MMP10 and MMP13 expression. Oncotarget 35 27172796
2015 SENP2 regulates MMP13 expression in a bladder cancer cell line through SUMOylation of TBL1/TBLR1. Scientific reports 34 26369384
2015 Infiltrating neutrophils increase bladder cancer cell invasion via modulation of androgen receptor (AR)/MMP13 signals. Oncotarget 34 26517808
2019 RECK suppresses interleukin-17/TRAF3IP2-mediated MMP-13 activation and human aortic smooth muscle cell migration and proliferation. Journal of cellular physiology 33 31074012
2017 MMP-2 and MMP-13 affect vasculogenic mimicry formation in large cell lung cancer. Journal of cellular and molecular medicine 33 28766880
2019 Activation of the P38/CREB/MMP13 axis is associated with osteoarthritis. Drug design, development and therapy 32 31308631
2013 Knee loading reduces MMP13 activity in the mouse cartilage. BMC musculoskeletal disorders 31 24180431
2017 Autophagy Protects Advanced Glycation End Product-Induced Apoptosis and Expression of MMP-3 and MMP-13 in Rat Chondrocytes. BioMed research international 30 28265573
2006 Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease. Scandinavian journal of gastroenterology 30 16938718
2019 Golgi Membrane Protein 1 (GOLM1) Promotes Growth and Metastasis of Breast Cancer Cells via Regulating Matrix Metalloproteinase-13 (MMP13). Medical science monitor : international medical journal of experimental and clinical research 29 30695018
2007 Transcriptional regulation of MMP13 by Lef1 in chondrocytes. Biochemical and biophysical research communications 29 17971297
2024 Chondrocyte-Targeted Delivery System of Sortase A-Engineered Extracellular Vesicles Silencing MMP13 for Osteoarthritis Therapy. Advanced healthcare materials 28 38545904
2018 Protein kinase D3 modulates MMP1 and MMP13 expression in human chondrocytes. PloS one 27 29652915
2019 Matrix metalloproteinases MMP-1, MMP-2, and MMP-13 are overexpressed in primary nodular melanoma. Journal of cutaneous pathology 26 31677173
2016 High molecular weight hyaluronic acid regulates MMP13 expression in chondrocytes via DUSP10/MKP5. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 26 27101204
2010 p38gamma mitogen-activated protein kinase suppresses chondrocyte production of MMP-13 in response to catabolic stimulation. Osteoarthritis and cartilage 26 20633667
2020 CircTMBIM6 promotes osteoarthritis-induced chondrocyte extracellular matrix degradation via miR-27a/MMP13 axis. European review for medical and pharmacological sciences 25 32767318
2019 circRNA‑CER mediates malignant progression of breast cancer through targeting the miR‑136/MMP13 axis. Molecular medicine reports 25 30816475
2018 Design, cyclization, and optimization of MMP13-TIMP1 interaction-derived self-inhibitory peptides against chondrocyte senescence in osteoarthritis. International journal of biological macromolecules 25 30352228
2014 Shedding of NG2 by MMP-13 attenuates anoikis. DNA and cell biology 25 25166220
2023 miR-99b-3p/Mmp13 axis regulates NLRP3 inflammasome-dependent microglial pyroptosis and alleviates neuropathic pain via the promotion of autophagy. International immunopharmacology 24 38061116
2015 Suppressed invasive and migratory behaviors of SW1353 chondrosarcoma cells through the regulation of Src, Rac1 GTPase, and MMP13. Cellular signalling 24 26303573
2022 CXCL8, MMP12, and MMP13 are common biomarkers of periodontitis and oral squamous cell carcinoma. Oral diseases 23 36321868
2022 Semaphorin 3A-Neuropilin-1 Signaling Modulates MMP13 Expression in Human Osteoarthritic Chondrocytes. International journal of molecular sciences 23 36430655
2008 Hsp90{beta} and p130(cas): novel regulatory factors of MMP-13 expression in human osteoarthritic chondrocytes. Annals of the rheumatic diseases 23 18593760
2016 MMP-13 is one of the critical mediators of the effect of HDAC4 deletion on the skeleton. Bone 22 27320207
2015 The Expression and Significance of CXCR5 and MMP-13 in Colorectal Cancer. Cell biochemistry and biophysics 22 25726157
2018 CCL17-CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer. Journal of cellular biochemistry 21 30230587
2015 Interleukin-32 stimulates osteosarcoma cell invasion and motility via AKT pathway-mediated MMP-13 expression. International journal of molecular medicine 21 25846944
2015 Cyclosporine A Downregulates MMP-3 and MMP-13 Expression in Cultured Pterygium Fibroblasts. Cornea 20 26057330
2015 Selective regulation of Mmp13 by 1,25(OH)2D3, PTH, and Osterix through distal enhancers. The Journal of steroid biochemistry and molecular biology 20 26348136
2008 Ultrasound stimulates MMP-13 expression through p38 and JNK pathway in osteoblasts. Journal of cellular physiology 20 17941091
2020 Tgfb3 and Mmp13 regulated the initiation of liver fibrosis progression as dynamic network biomarkers. Journal of cellular and molecular medicine 19 33269546
2023 MMP13-Overexpressing Mesenchymal Stem Cells Enhance Bone Tissue Formation in the Presence of Collagen Hydrogel. Tissue engineering and regenerative medicine 18 37041434
2019 Co-expression of TLR-9 and MMP-13 is associated with the degree of tumour differentiation in prostate cancer. International journal of experimental pathology 18 31090157
2018 Effects of Controlling Abnormal Joint Movement on Expression of MMP13 and TIMP-1 in Osteoarthritis. Cartilage 18 29938527
2016 The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070. Scientific reports 18 27245877
2015 Activity of MMP1 and MMP13 and amino acid metabolism in patients with alcoholic liver cirrhosis. Medical science monitor : international medical journal of experimental and clinical research 18 25863779

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