Affinage

MMP8

Neutrophil collagenase · UniProt P22894

Length
467 aa
Mass
53.4 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MMP-8 (collagenase-2) is a zinc-dependent, secreted endopeptidase that couples fibrillar collagen turnover to the proteolytic control of immune and adhesion signaling, with roles spanning wound repair, innate inflammation, blood-brain barrier integrity, tumor suppression, and stress-induced CNS remodeling (PMID:17375198, PMID:28330493). Its archetypal activity is cleavage of intact type I collagen into characteristic 3/4 products, and it is the predominant active collagenase in healing wounds and in dentin (PMID:9927539, PMID:17045563). Beyond matrix, MMP-8 processes a defined set of non-matrix substrates with distinct functional consequences: it activates the CXC chemokines LIX/CXCL5, CXCL8/IL-8 and ENA-78 by N-terminal cleavage to drive CXCR2-dependent neutrophil chemotaxis in a feed-forward inflammatory loop (PMID:17375198); it cleaves IL-10, and in its absence intact IL-10 sustains STAT3 signaling to suppress collagen synthesis and confer resistance to lung fibrosis (PMID:20949050); it cleaves the tight-junction protein occludin to increase BBB permeability during meningococcal infection (PMID:20442866); and it cleaves the anti-adhesive glycoprotein FXYD5, increasing cell-cell adhesion and reducing carcinoma migration (PMID:34059618). The enzyme's tumor-suppressive functions are strictly catalytic: somatic melanoma mutations that reduce activity abolish suppression of anchorage-independent growth, and a catalytically inactive mutant fails to promote integrin/hemidesmosome localization, restrain TGF-β signaling, or inhibit breast cancer invasion (PMID:19330028, PMID:28330493). Pro-MMP-8 is activated by MMP-7 cleavage, and MMP-8 forms specific complexes with MMP-9 in vivo with reciprocal compensatory regulation (PMID:17392479, PMID:17017992). Although produced predominantly by neutrophils and monocytes, MMP-8 is also synthesized by fibroblasts, odontoblasts, and epithelial cells, and stress-mobilized monocyte-derived MMP-8 infiltrates the nucleus accumbens to remodel extracellular space and drive social-avoidance behavior (PMID:10690664, PMID:38326622).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1999 Medium

    Established which collagenase dominates human wound repair and that its activation state, not mere abundance, distinguishes healing from chronic wounds.

    Evidence ELISA quantification and substrate-preference collagenase assays in human wound fluids and ulcer tissue

    PMID:9927539

    Open questions at the time
    • Correlative human tissue data without direct causal manipulation
    • Source cell type of the active enzyme not resolved here
  2. 2001 Medium

    Defined MMP-8 expression in development, identifying it as the first fibrillar collagenase active in neural crest, ectoderm, and chondrocytes, and noting re-expression in melanoma.

    Evidence RT-PCR, in situ hybridization, and immunohistochemistry of mouse embryos and human melanoma cell lines

    PMID:11731274

    Open questions at the time
    • Developmental function not tested by loss-of-function
    • Significance of melanoma re-expression unresolved at this stage
  3. 2006 High

    Identified non-neutrophil sources and an upstream activator: odontoblasts and dentin produce mesenchymal MMP-8, and MMP-7 proteolytically activates pro-MMP-8 in vivo.

    Evidence Western blot/IFMA detection in dentin with in vitro collagen cleavage; in vitro MMP-7 activation assay validated in MMP-7 knockout mouse ventricle

    PMID:17017992 PMID:17045563

    Open questions at the time
    • Relative contribution of MMP-7 versus other activators in vivo not quantified
    • Whether dentin MMP-8 is matrix-restricted unknown
  4. 2007 High

    Resolved the functionally relevant cellular source and a non-matrix mechanism in inflammation: bone-marrow/neutrophil MMP-8 drives wound closure and activates CXC chemokines to orchestrate neutrophil recruitment.

    Evidence Mmp8-null mouse wound and LPS models with bone-marrow-transplant rescue; in vitro recombinant chemokine cleavage with mapped sites, calcium and chemotaxis assays; in vivo MMP-8/MMP-9 complex detection

    PMID:17375198 PMID:17392479

    Open questions at the time
    • Functional consequence of the MMP-8/MMP-9 complex not mechanistically defined
    • Extent of compensatory MMP-9 upregulation across tissues unknown
  5. 2009 High

    Demonstrated that MMP-8 tumor suppression requires catalytic activity, by showing melanoma-derived loss-of-function mutations abolish suppression of anchorage-independent growth and tumor formation.

    Evidence Mutational and enzyme-activity analysis with soft-agar and xenograft assays for wild-type versus mutant MMP-8

    PMID:19330028

    Open questions at the time
    • The substrate(s) mediating suppression not identified in this study
    • Mechanism downstream of cleavage unaddressed
  6. 2010 High

    Defined two distinct non-matrix substrate axes — occludin cleavage controlling barrier integrity, and IL-10 cleavage controlling fibrosis via STAT3.

    Evidence MMP-8 siRNA and inhibitor studies with occludin fragment detection and BBB permeability assays; in vitro IL-10 cleavage with Mmp8-null bleomycin fibrosis model and IL-10-blockade rescue

    PMID:20442866 PMID:20949050

    Open questions at the time
    • Whether occludin and IL-10 cleavage occur in the same physiological settings unknown
    • In vivo cleavage site mapping of IL-10 not established
  7. 2017 High

    Mechanistically unified MMP-8 tumor suppression in epithelium: catalytically active MMP-8 in myoepithelial cells promotes integrin/hemidesmosome adhesion, dampens TGF-β and MMP-9 activity, and restrains invasion.

    Evidence Active-site mutant (MMP-8 EA) and siRNA in myoepithelial cells with adhesion, integrin localization, TGF-β, gelatinase, and 3D organotypic invasion assays

    PMID:28330493

    Open questions at the time
    • Direct substrate linking MMP-8 to integrin localization not identified here
    • TGF-β suppression mechanism indirect
  8. 2021 High

    Identified FXYD5 as a direct MMP-8 substrate by unbiased proteomics, explaining the adhesion/migration phenotype in oral carcinoma.

    Evidence TAILS proteomics with LC-MS/MS, in vitro recombinant cleavage, membrane FXYD5 immunofluorescence, and inhibitor rescue in tongue carcinoma cells

    PMID:34059618

    Open questions at the time
    • Cleavage site within FXYD5 not mapped here
    • In vivo relevance to tumor progression not tested
  9. 2024 High

    Extended MMP-8 function to a peripheral-to-CNS axis, showing stress-mobilized monocyte-derived MMP-8 enters the nucleus accumbens, remodels extracellular space, and drives social-avoidance behavior.

    Evidence Chronic social-defeat mouse model with mass cytometry, scRNA-seq, genetic/pharmacological MMP-8 depletion, infiltration tracking, electrophysiology, and EM

    PMID:38326622

    Open questions at the time
    • Molecular substrate within the NAc extracellular space not identified
    • Mechanism of MMP-8 brain entry incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MMP-8 substrate selection is partitioned across its many proteolytic targets (collagen, chemokines, IL-10, occludin, FXYD5, INSR) in specific cell and tissue contexts remains unresolved.
  • No structural model distinguishing matrix versus non-matrix substrate engagement
  • Context-dependent activation and localization mechanisms unclear
  • In vivo validation lacking for several candidate substrates (e.g. INSR)

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 3 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
MMP7MMP9

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. In healing wounds MMP-8 is present almost exclusively in its inactive form, whereas in nonhealing ulcers significant levels of the active form are present alongside reduced TIMP-1. ELISA quantification of MMP-1, MMP-8, and TIMP-1 in wound fluids and tissues; functional collagenase activity assay with substrate preference The Journal of surgical research Medium 9927539
2006 MMP-8 (collagenase-2) is the major collagenase in human dentin; it cleaves intact type I collagen into characteristic 3/4(alphaA)-cleavage products in vitro. No other collagenases (MMP-1, MMP-13) or cathepsin K were detected in dentin. Western blotting with collagenase-specific antibodies, immunofluorometric assay (IFMA), in vitro type I collagen degradation assay Archives of oral biology High 17045563
2007 MMP-8 deficiency (Mmp8-null mice) delays wound closure and alters inflammatory response. The wound-healing defect was rescued by bone marrow transplantation from wild-type mice, establishing that neutrophil/bone-marrow-derived MMP-8 is the functionally relevant source. MMP-8 and MMP-9 form specific complexes in vivo, and absence of MMP-8 leads to compensatory up-regulation of MMP-9. MMP8-/- knockout mouse wound-healing model, bone marrow transplantation rescue, in vivo co-immunoprecipitation (complex detection), Western blotting, histology FASEB journal High 17392479
2007 MMP-8 cleaves the CXC chemokine LIX at Ser4-Val5 and Lys79-Arg80, activating it; N-terminal cleavage of LIX increases intracellular calcium mobilization and neutrophil chemotaxis via CXCR2. MMP-8 also cleaves human CXCL8/IL-8 at Arg5-Ser6 and CXCL5/ENA-78 at Val7-Leu8, activating these chemokines. PMN-derived MMP-8 thus executes an in cis feed-forward mechanism to orchestrate initial innate inflammatory responses. Mmp8-null mouse in vivo LPS-challenge model, in vitro biochemical cleavage assays with recombinant proteins, calcium mobilization assay, chemotaxis assay with synthetic LIX analogues PloS one High 17375198
2009 Five somatic mutations in MMP8 found in human melanomas reduce MMP-8 enzyme activity. Expression of wild-type but not mutant MMP8 in melanoma cells inhibited anchorage-independent growth in vitro and tumor formation in vivo, indicating MMP-8 enzymatic activity is required for its tumor-suppressive function. Mutational analysis, enzyme activity assays of wild-type vs. mutant MMP-8, soft agar colony formation assay, xenograft tumor formation in vivo Nature genetics High 19330028
2010 MMP-8 activity in Neisseria meningitidis-infected brain microvascular endothelial cells (HBMEC) cleaves the tight junction protein occludin, producing a 50-kDa fragment, causing its disappearance from the cell periphery and increasing BBB permeability. MMP-8 also mediates cell detachment from the underlying matrix. Abrogation of MMP-8 by inhibitors or siRNA knockdown prevented occludin cleavage and partially restored BBB integrity. MMP-8 siRNA knockdown, specific MMP-8 inhibitors, Western blotting for occludin cleavage fragments, immunofluorescence, permeability assays, cell adhesion assays PLoS pathogens High 20442866
2010 MMP-8 cleaves murine and human IL-10 in vitro, and Mmp8-null mice show decreased IL-10 processing and increased unprocessed IL-10 levels. In the absence of MMP-8, increased intact IL-10 activates STAT3 signaling in lung fibroblasts, suppressing collagen synthesis and conferring resistance to bleomycin-induced lung fibrosis. Blockade of IL-10 in knockout mice restored collagen synthesis. In vitro IL-10 cleavage assay with recombinant MMP-8, Mmp8-/- knockout mouse bleomycin fibrosis model, Western blotting for IL-10 and STAT3 phosphorylation, cell culture experiments with IL-10 blockade PloS one High 20949050
2004 Three SNPs in the MMP8 promoter (-799C/T, -381A/G, +17C/G) form functionally significant haplotypes: the minor allele haplotype displays 3-fold greater promoter activity in trophoblast cells compared with the major allele haplotype. Electrophoretic mobility shift assays showed differences in nuclear protein binding at the -381 and -799 SNP positions. Reporter gene (promoter activity) assay in trophoblast cell lines, electrophoretic mobility shift assay (EMSA), case-control association study Human molecular genetics Medium 15367487
2003 MMP-8 expression in head and neck squamous cell carcinoma cells is down-regulated (~30-60%) by TGF-β1 and up-regulated (~2-2.5-fold) by phorbol 12-myristate 13-acetate (PMA), demonstrating cytokine and phorbol ester regulation of MMP-8 expression in carcinoma cells. Western blotting of conditioned culture media, semi-quantitative RT-PCR, immunohistochemistry, in situ hybridization The Journal of pathology Medium 12081207
2000 TGF-β1 (10 ng/mL) down-regulates MMP-8 mRNA expression and secreted protein concentration in human odontoblast and pulp tissue cultures. Odontoblasts express, synthesize, and secrete mesenchymal-type MMP-8 (50-kDa active form), establishing these cells as a non-neutrophil source. RT-PCR, Southern blot, Western blotting, immunofluorometric assay, immunohistochemistry, cell culture with TGF-β1 treatment Journal of dental research Medium 10690664
2016 MMP-8 and TGF-β1 engage in reciprocal positive regulation in hepatocellular carcinoma cells: MMP-8 overexpression restores TGF-β1 expression in TGF-β1-depleted cells, and TGF-β1 treatment restores MMP-8 expression in MMP-8-depleted cells, both acting primarily through the PI3K/Akt/Rac1 pathway. This mutual activation promotes EMT, migration, and invasion. MMP-8 overexpression and depletion in HCC cell lines, TGF-β1 treatment/depletion, Western blotting for PI3K/Akt/Rac1 pathway components and EMT markers, migration/invasion assays Cancer letters Medium 26872724
2006 MMP-7 (matrilysin) processes pro-MMP-8 to its active form in vitro. In MMP-7 knockout mouse left ventricles, MMP-8 levels increased while MMP-13 levels decreased in vivo, establishing MMP-8 as an in vivo substrate of MMP-7 and suggesting reciprocal regulatory interplay between MMP-8 and MMP-13. In vitro activation assay using recombinant active MMP-7 and pro-MMP-8, MMP-7 knockout mouse analysis by Western blotting Medicinal chemistry High 17017992
2016 In vitro, MMP-8 degrades the insulin receptor (INSR), and this cleavage is inhibited by the MMP inhibitors doxycycline and Ilomastat/GM6001, suggesting MMP-8-mediated cleavage of INSR as a mechanism linking elevated MMP-8 in obesity to insulin resistance. In vitro cleavage assay of recombinant INSR by MMP-8, inhibition by doxycycline and Ilomastat assessed by SDS-PAGE; serum MMP-8 measured by immunofluorometric assay in human twin cohort European journal of clinical investigation Medium 27296149
2020 Macrophage-derived MMP-8 promotes smooth muscle cell (SMC) differentiation from adventitia stem/progenitor cells (AdSPCs) through modulation of TGF-β activity and ADAM10/Notch1 signaling. The CSL binding site within SMC gene promoters mediates Notch1-driven SMC differentiation. MMP-8 from macrophages increases injury-induced neointimal SMC hyperplasia via ADAM10/Notch1 signaling. Macrophage/AdSPC co-culture, conditioned medium studies, macrophage-specific MMP-8 expression manipulation, Notch1 pathway analysis, CSL promoter analysis, in vivo arterial injury model in ApoE KO mice Cardiovascular research Medium 30778537
2024 Stress-induced circulating MMP-8, derived from peripheral monocytes, directly infiltrates the nucleus accumbens (NAc) parenchyma, controls the ultrastructure of the extracellular space, and induces neurophysiological changes. MMP-8 depletion prevented stress-induced social avoidance behaviour and NAc alterations, establishing a direct peripheral-to-CNS mechanism. Chronic social defeat stress mouse model, mass cytometry, single-cell RNA sequencing, pharmacological/genetic MMP-8 depletion, direct MMP-8 brain infiltration tracking, electrophysiology, electron microscopy of extracellular space Nature High 38326622
2013 MMP-8 is one of the key factors responsible for the release of TRAIL from polymorphonuclear neutrophils (PMNs) in response to bacterial stimulation (BCG or Clostridium butyricum MIYAIRI 588), and TLR2/4 signaling is important upstream of MMP-8-mediated TRAIL release. PMN stimulation with bacteria, MMP-8 inhibition experiments, TRAIL quantification in supernatants and lysates, in vitro and in vivo antitumor assays International journal of oncology Medium 23354042
2017 MMP-8 expressed by normal myoepithelial cells (MECs) increases MEC adhesion to extracellular matrix and reduces migration in a catalytic-activity-dependent manner (MMP-8 EA catalytically inactive mutant has no effect). MMP-8 promotes α6β4 integrin localization to hemidesmosomes, reduces TGF-β signaling, suppresses MMP-9 gelatinolytic activity, and inhibits breast cancer cell invasion. Loss of MMP-8 in DCIS-associated MECs enhances cancer cell invasion. Transfection with MMP-8 WT and catalytically inactive MMP-8 EA mutant, siRNA knockdown, adhesion/migration assays, integrin hemidesmosome localization, TGF-β signaling assays, gelatinase activity assays, 2D and 3D organotypic invasion assays Breast cancer research High 28330493
2021 MMP-8 cleaves FXYD5 (an anti-adhesive glycoprotein) in oral tongue squamous cell carcinoma cells, as confirmed by in vitro cleavage of recombinant proteins and TAILS proteomics. MMP-8-mediated FXYD5 cleavage reduces FXYD5 at the cell membrane, increases cell-cell adhesion, and diminishes cancer cell migration. Inhibition of MMP-8 proteolytic activity rescues FXYD5 membrane levels. TAILS proteomics (terminal amine isotopic labelling of substrates) with LC-MS/MS to identify substrates, in vitro recombinant protein cleavage assay, immunofluorescence for membrane FXYD5, cell adhesion and migration assays, MMP-8 inhibitor treatment, FXYD5 siRNA knockdown Oncogenesis High 34059618
2001 MMP-8 is expressed during early mouse embryonic development (E9.5–E14.5) in neural crest cells, surface ectoderm, and chondrocytes, being the first fibrillar collagenase expressed during development; post-partum expression is restricted. Adult human melanoma cells and melanoma cell lines also express MMP-8, contrasting with primary neonatal melanocytes. RT-PCR of mouse embryos, in situ hybridization, immunohistochemistry of embryonic sections and melanoma cell lines Matrix biology Medium 11731274
2001 Phorbol-12-myristate-13-acetate, IL-6, and TNF-α (alone and combined with heparin) potently upregulate MMP-8 and MMP-13 expression (up to 9-fold) in the RPMI 8226 myeloma cell line, demonstrating cytokine- and tumor promoter-mediated regulation of MMP-8 in plasma cells. Western blotting, semi-quantitative RT-PCR of myeloma cell line stimulated with cytokines and PMA The Journal of pathology Low 11400151
2009 Prevotella intermedia-induced upregulation of MMP-8 in human periodontal ligament cells is mediated through the p38 MAPK signaling pathway (p38 inhibitor SB203580 markedly inhibited MMP-8 expression), while MMP-1 upregulation proceeds via ERK and JNK pathways. Cyclooxygenase inhibitor indomethacin attenuates both, implicating prostaglandin E2 as an upstream mediator. Semi-quantitative RT-PCR, ELISA, Western blot of PDL cells stimulated with P. intermedia supernatant; pathway inhibitors (indomethacin, PD98059, SP600125, SB203580) FEMS microbiology letters Medium 19708869
2019 A bioengineered bilayered living cell construct (BLCC) upregulates fibroblast-derived MMP-8 collagenase and promotes endogenous release of MMP-activating zinc (via metallothioneins) in venous leg ulcer beds, activating an antifibrotic remodeling program and shifting nonhealing to healing phenotype. Randomized controlled clinical trial with biopsy transcriptomics (genomic profiling), functional analysis of wound bed biopsies, metallothionein and MMP-8 expression analysis Wound repair and regeneration Medium 31674093
2015 Melittin (bee venom peptide) inhibits TNF-α-induced MMP-1 and MMP-8 protein expression in chondrocytes by suppressing NF-κB and AP-1 transcription factor activities, and by inhibiting phosphorylation of Akt, JNK, and ERK1/2 (but not p38). Western blotting for MMP-1 and MMP-8 protein expression, NF-κB and AP-1 reporter gene assays, EMSA, Western blotting for kinase phosphorylation in TNF-α-stimulated C57BL/6 chondrocytes International immunopharmacology Medium 25708656

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. The Journal of surgical research 251 9927539
2006 Matrix metalloproteinase-8 (MMP-8) is the major collagenase in human dentin. Archives of oral biology 250 17045563
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
2007 Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 216 17392479
2002 Collagenase-2 (MMP-8) and collagenase-3 (MMP-13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue. Journal of clinical periodontology 199 11940142
2007 LPS responsiveness and neutrophil chemotaxis in vivo require PMN MMP-8 activity. PloS one 176 17375198
2010 Salivary MMP-8, TIMP-1, and ICTP as markers of advanced periodontitis. Journal of clinical periodontology 153 20507371
2010 Neisseria meningitidis induces brain microvascular endothelial cell detachment from the matrix and cleavage of occludin: a role for MMP-8. PLoS pathogens 142 20442866
2024 Circulating myeloid-derived MMP8 in stress susceptibility and depression. Nature 127 38326622
2009 Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy. Journal of clinical periodontology 123 19995403
2009 Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma. Nature genetics 120 19330028
2000 The expression of MMP-8 in human odontoblasts and dental pulp cells is down-regulated by TGF-beta1. Journal of dental research 114 10690664
2004 Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM). Human molecular genetics 109 15367487
2002 Airway obstruction correlates with collagenase-2 (MMP-8) expression and activation in bronchial asthma. Laboratory investigation; a journal of technical methods and pathology 102 12429813
2001 Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions. The Journal of pathology 100 11400151
2003 Levels and molecular forms of MMP-7 (matrilysin-1) and MMP-8 (collagenase-2) in diseased human peri-implant sulcular fluid. Journal of periodontal research 98 14632921
2010 Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10. PloS one 92 20949050
2005 Intraplaque MMP-8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound. Atherosclerosis 86 16259988
2001 In vivo collagenase-2 (MMP-8) expression by human bronchial epithelial cells and monocytes/macrophages in bronchiectasis. The Journal of pathology 86 11400153
2003 Expression of MMP-8 and MMP-13 genes in the periodontal ligament during tooth movement in rats. Journal of dental research 81 12885852
2019 The Role of MMP8 in Cancer: A Systematic Review. International journal of molecular sciences 80 31514474
2021 The RING E3 ligase CLG1 targets GS3 for degradation via the endosome pathway to determine grain size in rice. Molecular plant 79 34216830
2017 Salivary Diagnostics-Point-of-Care diagnostics of MMP-8 in dentistry and medicine. Diagnostics (Basel, Switzerland) 76 28117682
2006 Expression of matrix metalloproteinases (MMP-8 and -9) in chronic periodontitis patients with and without diabetes mellitus. Journal of periodontology 74 17076603
2006 Tear fluid levels of MMP-8 are elevated in ocular rosacea--treatment effect of oral doxycycline. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 72 16411105
2016 Reciprocal activation between MMP-8 and TGF-β1 stimulates EMT and malignant progression of hepatocellular carcinoma. Cancer letters 71 26872724
2003 Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer. European journal of cancer (Oxford, England : 1990) 71 14602136
2013 Clostridium butyricum MIYAIRI 588 shows antitumor effects by enhancing the release of TRAIL from neutrophils through MMP-8. International journal of oncology 68 23354042
2017 Comparison of rapid MMP-8 and interleukin-6 point-of-care tests to identify intra-amniotic inflammation/infection and impending preterm delivery in patients with preterm labor and intact membranes. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 65 28081646
2005 Carvedilol improves left ventricular function in murine coxsackievirus-induced acute myocarditis association with reduced myocardial interleukin-1beta and MMP-8 expression and a modulated immune response. European journal of heart failure 62 15921778
2003 Expression of matrix metalloproteinase 8 (MMP-8) and tyrosinase-related protein-1 (TYRP-1) correlates with the absence of metastasis in an isogenic human breast cancer model. Differentiation; research in biological diversity 61 12641565
2024 Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing. Journal of controlled release : official journal of the Controlled Release Society 60 38909697
2008 Plasma MMP1 and MMP8 expression in breast cancer: protective role of MMP8 against lymph node metastasis. BMC cancer 60 18366705
2007 Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 59 17244319
2002 Up-regulation of MMP-8 and MMP-9 activity in the BALB/c mouse spinal cord correlates with the severity of experimental autoimmune encephalomyelitis. Clinical and experimental immunology 59 11985514
2002 Expression and regulation of collagenase-2 (MMP-8) in head and neck squamous cell carcinomas. The Journal of pathology 58 12081207
2020 Effects of Albumin Infusion on Serum Levels of Albumin, Proinflammatory Cytokines (TNF-α, IL-1, and IL-6), CRP, and MMP-8; Tissue Expression of EGRF, ERK1, ERK2, TGF-β, Collagen, and MMP-8; and Wound Healing in Sprague Dawley Rats. International journal of inflammation 57 32518615
2016 Association of MMP-8 with obesity, smoking and insulin resistance. European journal of clinical investigation 57 27296149
2009 Prevotella intermedia upregulates MMP-1 and MMP-8 expression in human periodontal ligament cells. FEMS microbiology letters 50 19708869
2009 Gingival crevicular fluid MMP-8 and -13 and TIMP-1 levels in patients with rheumatoid arthritis and inflammatory periodontal disease. Journal of periodontology 49 19656031
2003 Gelatinase A (MMP-2), collagenase-2 (MMP-8), and laminin-5 gamma2-chain expression in murine inflammatory bowel disease (ulcerative colitis). Digestive diseases and sciences 49 12645796
2003 Laminin-5 gamma2-chain and collagenase-2 (MMP-8) in human peri-implant sulcular fluid. Clinical oral implants research 49 12656874
2018 High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer. British journal of cancer 48 29808017
2017 Salivary IgA, Interleukin-1β and MMP-8 as Salivary Biomarkers in Chronic Periodontitis Patients. The Chinese journal of dental research 45 28232966
2009 Activation of MMP8 and MMP13 by angiotensin II correlates to severe intra-plaque hemorrhages and collagen breakdown in atherosclerotic lesions with a vulnerable phenotype. Atherosclerosis 45 19233360
2021 sTREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity. Viruses 43 34960790
2008 Polymorphism +17 C/G in matrix metalloprotease MMP8 decreases lung cancer risk. BMC cancer 43 19094243
2002 Expression of MMP-8 and MMP-13 mRNAs in rat periodontium during tooth eruption. Journal of dental research 43 12351664
2016 MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations. Mediators of inflammation 40 27843200
2013 Induction of IL-6 and MMP-8 in human periodontal fibroblasts by static tensile strain. Clinical oral investigations 40 23851938
2016 MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath Condensate in COPD. COPD 39 27880043
2018 Anti-inflammatory and anti-oxidant mechanisms of an MMP-8 inhibitor in lipoteichoic acid-stimulated rat primary astrocytes: involvement of NF-κB, Nrf2, and PPAR-γ signaling pathways. Journal of neuroinflammation 38 30470240
2022 Active MMP-8 point-of-care (PoC)/chairside enzyme-test as an adjunctive tool for early and real-time diagnosis of peri-implantitis. Clinical and experimental dental research 37 35118828
2001 Neutrophil collagenase (MMP-8) is expressed during early development in neural crest cells as well as in adult melanoma cells. Matrix biology : journal of the International Society for Matrix Biology 37 11731274
2014 Mononuclear phagocytes and airway epithelial cells: novel sources of matrix metalloproteinase-8 (MMP-8) in patients with idiopathic pulmonary fibrosis. PloS one 34 24828408
2012 Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes. Journal of cellular physiology 34 21826658
2011 Matrix metalloproteinase 8 (MMP8) gene polymorphisms in chronic periodontitis. Archives of oral biology 34 21920499
2021 Elevated expression of MMP8 and MMP9 contributes to diabetic osteoarthritis progression in a rat model. Journal of orthopaedic surgery and research 33 33468174
2016 Assessment of MMP-1, MMP-8 and TIMP-2 in experimental periodontitis treated with kaempferol. Journal of periodontal & implant science 32 27127689
2011 Uncommon GNAQ, MMP8, AKT3, EGFR, and PIK3R1 mutations in thyroid cancers. Endocrine pathology 32 21487925
2021 Active MMP-8 Quantitative Test as an Adjunctive Tool for Early Diagnosis of Periodontitis. Diagnostics (Basel, Switzerland) 31 34441437
2017 Loss of MMP-8 in ductal carcinoma in situ (DCIS)-associated myoepithelial cells contributes to tumour promotion through altered adhesive and proteolytic function. Breast cancer research : BCR 31 28330493
2024 Importance of Metalloproteinase 8 (MMP-8) in the Diagnosis of Periodontitis. International journal of molecular sciences 30 38473967
2012 Use of MMP-8 and MMP-9 to assess disease severity in children with viral lower respiratory tract infections. Journal of medical virology 30 22825827
2007 Increased tissue factor, MMP-8, and D-dimer expression in diabetic patients with unstable advanced carotid atherosclerosis. Vascular health and risk management 30 17969370
2004 Effects of 17 beta-estradiol on the expression of interstitial collagenases-8 and -13 (MMP-8 and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in ovariectomized rat osteoblastic cells. Journal of molecular histology 30 15609084
2019 Salivary levels of MPO, MMP-8 and TIMP-1 are associated with gingival inflammation response patterns during experimental gingivitis. Cytokine 29 30626536
2015 Melittin has a chondroprotective effect by inhibiting MMP-1 and MMP-8 expressions via blocking NF-κB and AP-1 signaling pathway in chondrocytes. International immunopharmacology 29 25708656
2013 Matrix metalloproteinase (MMP)-8 and tissue inhibitor of MMP-1 (TIMP-1) gene polymorphisms in generalized aggressive periodontitis: gingival crevicular fluid MMP-8 and TIMP-1 levels and outcome of periodontal therapy. Journal of periodontology 29 24283658
2011 Associations of periodontal microorganisms with salivary proteins and MMP-8 in gingival crevicular fluid. Journal of clinical periodontology 29 22103335
2023 Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8. Chinese journal of natural medicines 28 37777317
2013 Expression and inhibition of matrix metalloproteinase (MMP)-8, MMP-9 and MMP-12 in early colonic anastomotic repair. International journal of colorectal disease 27 23619615
2011 Expression of MMP-8 and MMP-13 in the development of periradicular lesions. International endodontic journal 27 21447140
2020 Macrophage-derived MMP-8 determines smooth muscle cell differentiation from adventitia stem/progenitor cells and promotes neointima hyperplasia. Cardiovascular research 26 30778537
2015 MMP-7, MMP-8, and MMP-9 in oral and cutaneous squamous cell carcinomas. Oral surgery, oral medicine, oral pathology and oral radiology 26 25697929
2006 Matrix metalloproteinase (MMP)-7 activates MMP-8 but not MMP-13. Medicinal chemistry (Shariqah (United Arab Emirates)) 26 17017992
2019 A bioengineered living cell construct activates metallothionein/zinc/MMP8 and inhibits TGFβ to stimulate remodeling of fibrotic venous leg ulcers. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 25 31674093
2019 A Prototype Antibody-based Biosensor for Measurement of Salivary MMP-8 in Periodontitis using Surface Acoustic Wave Technology. Scientific reports 24 31363141
2012 Influence of MMP-8 promoter polymorphism in early osseointegrated implant failure. Clinical oral investigations 24 22382449
2023 Matrix Metalloproteinases in Oral Health-Special Attention on MMP-8. Biomedicines 23 37371608
2018 MMP8 and MMP9 gene polymorphisms were associated with breast cancer risk in a Chinese Han population. Scientific reports 23 30194384
1999 GCF levels of MMP-3 and MMP-8 following placement of bioresorbable membranes. Journal of clinical periodontology 23 10589813
2024 Single-cell analysis defines highly specific leukemia-induced neutrophils and links MMP8 expression to recruitment of tumor associated neutrophils during FGFR1 driven leukemogenesis. Experimental hematology & oncology 21 38730491
2013 Identification of a lifespan extending mutation in the Schizosaccharomyces pombe cyclin gene clg1+ by direct selection of long-lived mutants. PloS one 21 23874875
2012 Multiplex array proteomics detects increased MMP-8 in CSF after spinal cord injury. Journal of neuroinflammation 21 22687332
2021 Origin of MMP-8 and Lactoferrin levels from gingival crevicular fluid, salivary glands and whole saliva. BMC oral health 20 34353321
2019 Are MMP3, MMP8 and TIMP2 gene variants associated with anterior cruciate ligament rupture susceptibility? Journal of science and medicine in sport 20 30755371
2015 Correlation between peri-implant sulcular fluid rate and expression of collagenase2 (MMP8). Clinical oral investigations 20 26077894
2015 Association study of MMP8 gene in osteoarthritis. Connective tissue research 20 26577236
2014 MMP-8 genotypes influence the inflammatory response in human endotoxemia. Inflammation 20 24170307
2024 OsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate. Nature communications 19 38773134
2019 LncRNA KCNQ1OT1 contributes to oxygen-glucose-deprivation/reoxygenation-induced injury via sponging miR-9 in cultured neurons to regulate MMP8. Experimental and molecular pathology 19 31837324
2018 Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy. Histology and histopathology 19 29532899
2011 Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: preliminary study. Atherosclerosis 19 21906737
2015 Immunohistochemical expression of MMP-2 and MMP-8 in oral squamous cell carcinoma. Journal of clinical and experimental dentistry 18 26155333
2014 MMP7 and MMP8 genetic polymorphisms in bladder cancer patients. Central European journal of urology 18 24757528
2014 A natural bacterial-derived product, the metalloprotease arazyme, inhibits metastatic murine melanoma by inducing MMP-8 cross-reactive antibodies. PloS one 18 24788523
2018 MMP-3 and MMP-8 in rat mandibular condylar cartilage associated with dietary loading, estrogen level, and aging. Archives of oral biology 17 30412863
2021 MMP8 increases tongue carcinoma cell-cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5. Oncogenesis 16 34059618
2018 MicroRNA-2682-3p inhibits osteosarcoma cell proliferation by targeting CCND2, MMP8 and Myd88. Oncology letters 16 30127935

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