Affinage

ADAMTS3

A disintegrin and metalloproteinase with thrombospondin motifs 3 · UniProt O15072

Length
1205 aa
Mass
135.6 kDa
Annotated
2026-06-09
98 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAMTS3 is a secreted zinc metalloproteinase that shapes extracellular matrix and signaling processes across cartilage, the lymphatic vasculature, and the developing brain through substrate-specific proteolysis (PMID:11408482, PMID:28213441, PMID:28985353). It acts as a procollagen II N-propeptidase, rescuing N-propeptide processing in chondrosarcoma cells deficient in this activity (PMID:11408482). In the lymphatic axis it proteolytically activates pro-VEGFC, feeding the CCBE1/VEGFC/VEGFR3 lymphangiogenic pathway; bi-allelic loss-of-function missense mutations that cause abnormal intracellular sequestration of the enzyme and abolish pro-VEGFC activation cause Hennekam lymphangiectasia-lymphedema syndrome type 3 (PMID:28985353). This catalytic role is functionally shared with the close paralogs ADAMTS2 and ADAMTS14, which process pro-VEGFC as efficiently as ADAMTS3 and substitute for it in adult lymphatic homeostasis (PMID:35316211). In the cerebral cortex and hippocampus, ADAMTS3 is the principal Reelin-inactivating protease, cleaving Reelin within repeat 3, and its loss in excitatory forebrain neurons increases dendritic branching and elongation, with downstream consequences for the Reelin/amyloid-β axis (PMID:28213441, PMID:30828067). ADAMTS3 also degrades fibronectin to restrain integrin α5β1-driven invasion, acting as a tumour suppressor in early breast cancer (PMID:37336268). Its transcription is controlled by USF1 (repressor) and induced by TNF-α/NF-κB/STAT3 and VEGF/hypoxia signaling (PMID:34432781, PMID:42083632, PMID:42224870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Established that ADAMTS3 possesses procollagen II N-propeptidase activity, defining its first known catalytic substrate and placing it among the procollagen-processing ADAMTS enzymes.

    Evidence Stable transfection of processing-defective RCS-LTC chondrosarcoma cells with human ADAMTS-3 and rescue of N-propeptide processing

    PMID:11408482

    Open questions at the time
    • Only partial rescue shown in one cell system
    • No kinetic characterization or cleavage-site mapping in this work
  2. 2001 Medium

    Showed that the closely related paralog ADAMTS14 can process procollagen aminopropeptide in the absence of ADAMTS2, raising the possibility of functional redundancy among ADAMTS2/3/14 procollagen N-propeptidases.

    Evidence Cloning of ADAMTS-14 and procollagen I aminopropeptide processing in ADAMTS-2-deficient context

    PMID:11741898

    Open questions at the time
    • ADAMTS3 activity itself not directly re-tested here
    • Redundancy inferred by homology rather than demonstrated for ADAMTS3
  3. 2017 High

    Identified ADAMTS3 as the major Reelin-inactivating protease in cortex and hippocampus, connecting its proteolysis to neuronal Reelin signaling and dendritic development.

    Evidence Biochemical purification from cortical neuron conditioned medium, recombinant cleavage assay, and full/conditional ADAMTS-3 knockout mice with Dab1, Tau phosphorylation, and dendritic morphology readouts

    PMID:28213441

    Open questions at the time
    • Other proteases contributing to residual Reelin cleavage not fully resolved
    • Structural basis of repeat-3 cleavage specificity not determined
  4. 2017 High

    Linked ADAMTS3 to human disease by showing loss-of-function mutations abolish pro-VEGFC activation, defining its role in the VEGFC/VEGFR3 lymphangiogenic axis.

    Evidence Whole-exome sequencing of an affected family plus in vitro processing, localization, and pro-VEGFC activation assays of mutant proteins

    PMID:28985353

    Open questions at the time
    • Mechanism of intracellular sequestration of mutant protein not detailed
    • Relationship between residual activity and phenotype severity unresolved
  5. 2019 Medium

    Placed ADAMTS3 within the Reelin/amyloid-β axis, showing that reducing its activity decreases Aβ deposition in an Alzheimer model.

    Evidence Drug-inducible conditional ADAMTS-3 knockout crossed with AppNL-F and AppNL-G-F knock-in mice; Aβ immunohistochemistry

    PMID:30828067

    Open questions at the time
    • Effect absent in Arctic-mutant Aβ background, limiting generality
    • Pathway placement via epistasis rather than direct biochemistry
  6. 2019 Low

    Associated an ADAMTS3 missense variant with canine upper airway syndrome, proposing a lymphoedema-driven mechanism but without functional validation.

    Evidence GWAS, whole-genome resequencing, and segregation analysis in Norwich Terriers and bulldogs

    PMID:31095560

    Open questions at the time
    • Functional consequence of the specific variant not experimentally tested
    • Causal mechanism inferred from prior literature only
  7. 2021 Medium

    Defined USF1 as a direct transcriptional repressor of ADAMTS3, opening study of its upstream regulation.

    Evidence Ectopic USF1 expression in osteosarcoma cells, promoter-reporter assays, and EMSA in Saos-2 and MG-63 cells

    PMID:34432781

    Open questions at the time
    • Physiological context where USF1 controls ADAMTS3 not established
    • Single lab, no in vivo validation
  8. 2022 High

    Demonstrated that ADAMTS2 and ADAMTS14 process pro-VEGFC as efficiently as ADAMTS3 and substitute for it in adult lymphatic homeostasis, refining the redundancy among the three enzymes.

    Evidence In vitro pro-VEGFC processing assays and single/double knockout mice with lymphatic vessel and corneal lymphangiogenesis assays

    PMID:35316211

    Open questions at the time
    • Developmental vs adult-specific contributions of each paralog not fully separated
    • Tissue-specific division of labor incompletely mapped
  9. 2023 Medium

    Identified fibronectin as an ADAMTS3 substrate and established a tumour-suppressive role in early breast cancer through restraint of integrin-driven invasion.

    Evidence TAILS degradomics, heterocellular spheroid invasion model, and integrin α5β1 blocking with ADAMTS3 loss-of-function

    PMID:37336268

    Open questions at the time
    • Direct cleavage-site verification of fibronectin not detailed
    • Single lab; in vivo tumour data not shown
  10. 2026 Medium

    Characterized inflammatory transcriptional induction of ADAMTS3 via MEK/PI3K/JNK/NF-κB and STAT3 signaling in osteosarcoma.

    Evidence Pharmacological pathway inhibitors, promoter-reporter assays, and TCGA co-expression analysis in osteosarcoma cell lines

    PMID:42083632

    Open questions at the time
    • Direct transcription-factor binding to promoter not all mapped
    • Functional consequence of induced ADAMTS3 in osteosarcoma not tested
  11. 2026 Medium

    Showed VEGF and hypoxia strongly induce ADAMTS3 in endothelial cells through defined promoter elements, creating a feed-forward link between VEGF signaling and the VEGFC-activating protease.

    Evidence CoCl2-induced hypoxia in HUVECs, VEGF stimulation, promoter-reporter assays with defined fragments, and pathway inhibitors

    PMID:42224870

    Open questions at the time
    • Specific transcription factors binding the VEGF-responsive elements not identified
    • In vivo relevance of the VEGF/hypoxia induction not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADAMTS3 substrate selectivity, subcellular processing, and tissue-specific deployment are coordinated across its collagen, VEGFC, Reelin, and fibronectin roles remains unresolved.
  • No structural model explaining multi-substrate specificity
  • Determinants partitioning ADAMTS3 vs ADAMTS2/14 between tissues unclear
  • Regulation of enzyme activity (vs transcription) post-secretion uncharacterized

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
Localization
GO:0005576 extracellular region 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-162582 Signal Transduction 2
Partners
FN1ITGA5RELNUSF1VEGFC

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 ADAMTS-3 has procollagen II N-propeptidase activity: stable transfection of RCS-LTC cells (which fail to process procollagen II N-propeptide) with human ADAMTS-3 partially rescued the processing defect, demonstrating that ADAMTS-3 can cleave the procollagen II N-propeptide. Stable transfection of RCS-LTC chondrosarcoma cells with human ADAMTS-3 expression construct; rescue of procollagen II N-propeptide processing assessed by cell biology assay The Journal of biological chemistry High 11408482
2017 ADAMTS-3 is the major protease that cleaves and inactivates Reelin in the cerebral cortex and hippocampus: recombinant ADAMTS-3 cleaved Reelin at the N-t site (within Reelin repeat 3); N-t cleavage was markedly decreased in ADAMTS-3 knockout mouse embryonic cerebral cortex; ADAMTS-3 is expressed in excitatory neurons; conditional KO of ADAMTS-3 in excitatory forebrain neurons increased dendritic branching and elongation postnatally. Partial purification and identification of the N-t Reelin-cleaving enzyme from cortical neuron conditioned medium; recombinant ADAMTS-3 cleavage assay; ADAMTS-3 knockout mice (full KO and conditional KO); immunohistochemistry; Dab1 and Tau phosphorylation quantification The Journal of neuroscience High 28213441
2017 Loss-of-function bi-allelic missense mutations in ADAMTS3 cause Hennekam lymphangiectasia-lymphedema syndrome type 3; the mutant proteins were abnormally processed and sequestered within cells, abolishing proteolytic activation of pro-VEGFC, linking ADAMTS3 to the CCBE1/VEGFC/VEGFR3 lymphangiogenic signaling axis. Whole-exome sequencing of affected family; in vitro characterization of mutant ADAMTS3 proteins (processing assay, cellular localization, pro-VEGFC activation assay) Human molecular genetics High 28985353
2001 ADAMTS-14, a paralog highly homologous to ADAMTS-2 and ADAMTS-3, can cleave the aminopropeptide of type I procollagen in vivo in the absence of ADAMTS-2 activity, suggesting that ADAMTS-3 (and ADAMTS-14) can substitute as procollagen aminopropeptidases. Cloning of ADAMTS-14 cDNA; in vivo processing of procollagen I aminopropeptide in ADAMTS-2-deficient context; recombinant ADAMTS-14 activity assay The Journal of biological chemistry Medium 11741898
2019 Reducing ADAMTS-3 inhibits amyloid-β deposition in AppNL-F knock-in mice (producing wild-type human Aβ), consistent with ADAMTS-3 inactivating Reelin whose activity opposes Aβ deposition; no effect was seen in AppNL-G-F mice producing Arctic mutant Aβ. Drug-inducible conditional ADAMTS-3 knockout mice crossed with AppNL-F and AppNL-G-F knock-in AD model mice; Aβ deposition quantified by immunohistochemistry Biological & pharmaceutical bulletin Medium 30828067
2022 ADAMTS2 and ADAMTS14 can process pro-VEGFC into active VEGFC as efficiently as ADAMTS3; adult Adamts2-KO mice develop skin lymphedema due to reduced lymphatic vessel density and diameter, while Adamts14-KO alone has no impact; double Adamts2/Adamts14-KO further reduces corneal lymphangiogenesis, indicating that ADAMTS2 and ADAMTS14 substitute for ADAMTS3 in adult lymphatic homeostasis. In vitro pro-VEGFC processing assay with recombinant ADAMTS2, ADAMTS14, and ADAMTS3; single and double gene knockout mice; lymphatic vessel density/diameter measurement; corneal lymphangiogenesis model JCI insight High 35316211
2023 ADAMTS3 mediates fibronectin degradation and acts as a tumour suppressor in early breast cancer: loss of ADAMTS3 in myoepithelial cells enhances fibronectin levels in the microenvironment, promoting invasion through integrin α5β1 activation; degradomic analysis (TAILS) identified fibronectin as an ADAMTS3 substrate. Heterocellular spheroid invasion model; TAILS (terminal amine isotopic labelling of substrates) degradomics; fibronectin functional assays; integrin α5β1 blocking experiments; ADAMTS3 loss-of-function Matrix biology Medium 37336268
2019 An ADAMTS3 missense variant (c.2786G>A in exon 20) is associated with Norwich Terrier Upper Airway Syndrome, and the risk allele is enriched in BOAS-susceptible French and English Bulldogs; the mechanism is proposed to be airway oedema caused by disruption of ADAMTS3 (lymphoedema pathway), predisposing to respiratory obstruction. Genome-wide association study; whole-genome resequencing; Sanger sequencing; segregation analysis in 401 Norwich Terriers PLoS genetics Low 31095560
2021 USF1 overexpression decreases ADAMTS-3 mRNA and protein expression in osteosarcoma cells and negatively regulates ADAMTS-3 promoter activity; EMSA studies showed USF1 directly binds to the ADAMTS-3 promoter region. Ectopic USF1 expression in Saos-2 and MG-63 cells; RT-PCR and western blot for ADAMTS-3; co-transfection promoter-reporter assay; electrophoretic mobility shift assay (EMSA) Molekuliarnaia biologiia Medium 34432781
2026 TNF-α induces ADAMTS-3 transcription in osteosarcoma cells via MEK, PI3K, JNK, and NF-κB pathways, with STAT3 and NF-κB enhancing ADAMTS-3 promoter activity; ADAMTS-3 expression correlates with ECM remodeling and inflammatory gene signatures in osteosarcoma. Pharmacological pathway inhibitors (MEK, PI3K, JNK, NF-κB) in osteosarcoma cell lines; promoter-reporter assays; TCGA genomic and transcriptomic analysis; co-expression analysis Journal of cell communication and signaling Medium 42083632
2026 VEGF₁₆₅ robustly enhances ADAMTS3 expression in endothelial cells (~46-fold at 3 h); hypoxia amplifies this VEGF response; defined ADAMTS3 promoter fragments (-131/+40; -1340/+40) show strong VEGF responsiveness under hypoxic conditions; JNK, MAPK/ERK, p38, and PI3K pathways each partially contribute to VEGF-mediated ADAMTS3 transcription. CoCl₂-induced hypoxia in HUVECs; VEGF stimulation; RT-PCR and protein expression; promoter-reporter assays with defined promoter fragments; pharmacological inhibitors of JNK, MAPK/ERK, p38, PI3K; RNA-seq analysis Tissue & cell Medium 42224870

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. The Journal of biological chemistry 389 11278559
2007 Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis and rheumatism 334 17265492
2003 IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 300 12568957
2004 Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice. Arthritis and rheumatism 245 15334469
2007 Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4. The Journal of biological chemistry 219 17430884
2000 Sites of aggrecan cleavage by recombinant human aggrecanase-1 (ADAMTS-4). The Journal of biological chemistry 197 10751421
2001 Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis. The Journal of biological chemistry 185 11408482
2003 Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing. The Journal of biological chemistry 176 14662755
2013 Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1 (ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-κB. The American journal of pathology 166 23602832
2000 The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage. The Journal of biological chemistry 163 10827174
2001 Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3. The Journal of biological chemistry 154 11741898
2002 Autocatalytic cleavage of ADAMTS-4 (Aggrecanase-1) reveals multiple glycosaminoglycan-binding sites. The Journal of biological chemistry 123 12202483
2007 ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of human atherosclerotic plaques. Atherosclerosis 100 17606262
2008 Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. Rheumatology international 90 18941754
2013 MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes. Arthritis research & therapy 89 23406982
2017 Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3. Human molecular genetics 83 28985353
2012 The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury. Journal of neuroinflammation 77 22420304
2014 Low density lipoprotein receptor-related protein 1 (LRP1)-mediated endocytic clearance of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4): functional differences of non-catalytic domains of ADAMTS-4 and ADAMTS-5 in LRP1 binding. The Journal of biological chemistry 76 24474687
2012 ADAMTS-1 and ADAMTS-4 levels are elevated in thoracic aortic aneurysms and dissections. The Annals of thoracic surgery 72 23245439
2017 Critical Role of ADAMTS-4 in the Development of Sporadic Aortic Aneurysm and Dissection in Mice. Scientific reports 70 28955046
2012 Regulated proteolytic processing of Reelin through interplay of tissue plasminogen activator (tPA), ADAMTS-4, ADAMTS-5, and their modulators. PloS one 69 23082219
2014 Leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 genes expression by mitogen-activated protein kinases and NF-ĸB signaling pathways in human chondrocytes. Cell biology international 65 25045124
2015 Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT). ACS medicinal chemistry letters 64 26288689
2017 Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 28213441
2013 Tumor necrosis factor-α induces ADAMTS-4 expression in human osteoarthritis chondrocytes. Molecular medicine reports 59 24126638
2007 TIMP-3 inhibition of ADAMTS-4 (Aggrecanase-1) is modulated by interactions between aggrecan and the C-terminal domain of ADAMTS-4. The Journal of biological chemistry 57 17470431
2005 ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms. Archives of biochemistry and biophysics 57 16289022
2010 Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications. The Biochemical journal 56 20645923
2006 Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines. Biochemical and biophysical research communications 52 16677612
2008 The regulation of aggrecanase ADAMTS-4 expression in human Achilles tendon and tendon-derived cells. Matrix biology : journal of the International Society for Matrix Biology 49 18387286
2004 Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins) from articular cartilage exposed to ADAMTS-4 (aggrecanase 1) or ADAMTS-5 (aggrecanase 2). Arthritis and rheumatism 43 15457452
2014 Upregulation of tumor necrosis factor α and ADAMTS-5, but not ADAMTS-4, in human intervertebral cartilage endplate with modic changes. Spine 42 24732836
2014 Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages. Genetics and molecular research : GMR 41 25501175
2010 Cytokine-induced increases in ADAMTS-4 messenger RNA expression do not lead to increased aggrecanase activity in ADAMTS-5-deficient mice. Arthritis and rheumatism 41 20662062
2016 Anti-inflammatory effects of ADAMTS-4 in a mouse model of ischemic stroke. Glia 38 27301579
2000 ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) is transcriptionally induced in beta-amyloid treated rat astrocytes. Neuroscience letters 38 10961658
2001 Distribution of aggrecanase (ADAMts 4/5) cleavage products in normal and osteoarthritic human articular cartilage: the influence of age, topography and zone of tissue. Osteoarthritis and cartilage 36 11520169
2006 Expression of ADAMTS-4 (aggrecanase-1) and possible involvement in regression of lumbar disc herniation. Spine 34 16741450
2015 CCN1 (Cyr61) Is Overexpressed in Human Osteoarthritic Cartilage and Inhibits ADAMTS-4 (Aggrecanase 1) Activity. Arthritis & rheumatology (Hoboken, N.J.) 33 25709087
2012 Anti-angiogenic properties of ADAMTS-4 in vitro. International journal of experimental pathology 33 22264287
2011 Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis. International journal of rheumatic diseases 32 22324945
2015 Association between ADAMTS-4 gene polymorphism and lumbar disc degeneration in Chinese Han population. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 31 26495885
2007 Substrate-dependent inhibition kinetics of an active site-directed inhibitor of ADAMTS-4 (Aggrecanase 1). Biochemistry 29 17487981
2020 MiR-126a-5p limits the formation of abdominal aortic aneurysm in mice and decreases ADAMTS-4 expression. Journal of cellular and molecular medicine 28 32469162
2017 Cleavage of Fibulin-2 by the aggrecanases ADAMTS-4 and ADAMTS-5 contributes to the tumorigenic potential of breast cancer cells. Oncotarget 28 28099917
2013 Assessment of the matrix degenerative effects of MMP-3, ADAMTS-4, and HTRA1, injected into a bovine intervertebral disc organ culture model. Spine 28 23778376
2007 Involvement of protein kinase Czeta in interleukin-1beta induction of ADAMTS-4 and type 2 nitric oxide synthase via NF-kappaB signaling in primary human osteoarthritic chondrocytes. Arthritis and rheumatism 28 18050214
2016 ADAMTS-4 promotes neurodegeneration in a mouse model of amyotrophic lateral sclerosis. Molecular neurodegeneration 27 26809777
2010 Transcript levels of major MMPs and ADAMTS-4 in relation to the clinicopathological profile of patients with lumbar disc herniation. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 27 20857147
2004 Effect of adenovirus-mediated overexpression of bovine ADAMTS-4 and human ADAMTS-5 in primary bovine articular chondrocyte pellet culture system. Osteoarthritis and cartilage 25 15262240
2018 IL-1β-induced miR-34a up-regulation inhibits Cyr61 to modulate osteoarthritis chondrocyte proliferation through ADAMTS-4. Journal of cellular biochemistry 21 29236314
2016 Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1. Molecular medicine reports 21 27082728
2005 Mammalian expression of full-length bovine aggrecan and link protein: formation of recombinant proteoglycan aggregates and analysis of proteolytic cleavage by ADAMTS-4 and MMP-13. Biochimica et biophysica acta 21 16427204
2012 Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines. International journal of oncology 20 22735305
2006 Effects of covalently attached chondroitin sulfate on aggrecan cleavage by ADAMTS-4 and MMP-13. Matrix biology : journal of the International Society for Matrix Biology 20 16945513
2018 Leptin induces MMP1/13 and ADAMTS 4 expressions through bone morphogenetic protein-2 autocrine effect in human chondrocytes. Journal of cellular biochemistry 18 29236309
2009 Adaptor proteins and Ras synergistically regulate IL-1-induced ADAMTS-4 expression in human chondrocytes. Journal of immunology (Baltimore, Md. : 1950) 18 19342688
2019 An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome. PLoS genetics 17 31095560
2022 ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in adults for pro-VEGFC activation and lymphatic homeostasis. JCI insight 16 35316211
2013 ADAMTS-4 and biglycan are expressed at high levels and co-localize to podosomes during endothelial cell tubulogenesis in vitro. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 16 24051360
2019 ADAMTS-9 in Mouse Cartilage Has Aggrecanase Activity That Is Distinct from ADAMTS-4 and ADAMTS-5. International journal of molecular sciences 15 30699963
2013 The development and characterization of a competitive ELISA for measuring active ADAMTS-4 in a bovine cartilage ex vivo model. Matrix biology : journal of the International Society for Matrix Biology 14 23295731
2022 First Characterization of ADAMTS-4 in Kidney Tissue and Plasma of Patients with Chronic Kidney Disease-A Potential Novel Diagnostic Indicator. Diagnostics (Basel, Switzerland) 13 35328201
2018 Depletion of aquaporin 1 decreased ADAMTS‑4 expression in human chondrocytes. Molecular medicine reports 12 29393494
2017 ADAMTS-4 in central nervous system pathologies. Journal of neuroscience research 12 28084617
2005 Genetic association analysis of the IGFBP7, ADAMTS3, and IL8 genes as the potential osteoarthritis susceptibility that maps to chromosome 4q. Annals of the rheumatic diseases 12 15708897
2023 ADAMTS3 restricts cancer invasion in models of early breast cancer progression through enhanced fibronectin degradation. Matrix biology : journal of the International Society for Matrix Biology 11 37336268
2017 The Absence of Detectable ADAMTS-4 (Aggrecanase-1) Activity in Synovial Fluid Is a Predictive Indicator of Autologous Chondrocyte Implantation Success. The American journal of sports medicine 11 28277753
2016 Pharmacophore development and screening for discovery of potential inhibitors of ADAMTS-4 for osteoarthritis therapy. Journal of molecular modeling 11 27401455
2014 ADAMTS-4 and ADAMTS-5 expression in human temporomandibular joint discs with internal derangement, correlates with degeneration. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 11 25477257
2019 Reducing ADAMTS-3 Inhibits Amyloid β Deposition in App Knock-in Mouse. Biological & pharmaceutical bulletin 10 30828067
2018 An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3. American journal of medical genetics. Part A 10 30450763
2016 ADAMTS-3, -13, -16, and -19 levels in patients with habitual abortion. The Kaohsiung journal of medical sciences 10 28088271
2019 Inhibition of ADAMTS-4 Expression in Olfactory Ensheathing Cells Enhances Recovery after Transplantation within Spinal Cord Injury. Journal of neurotrauma 9 31264504
2023 In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function. BMC bioinformatics 8 37322437
2022 ADAMTS-4 as a possible distinguishing indicator between osteoarthritis and haemophilic arthropathy. Haemophilia : the official journal of the World Federation of Hemophilia 7 35536550
2013 ADAMTS-4_v1 is a splice variant of ADAMTS-4 that is expressed as a protein in human synovium and cleaves aggrecan at the interglobular domain. Arthritis and rheumatism 7 23897278
2017 Correlation analysis of ADAMTS-4, VCAM-1, and TAK1 expression in cartilage tissue from spine tuberculosis. Genetics and molecular research : GMR 6 28829887
2022 Downregulation of ADAMTS3 Suppresses Stemness and Tumorigenicity in Glioma Stem Cell. CNS neuroscience & therapeutics 5 36514188
2019 The Effect of Mesenchymal Stem Cell Wharton's Jelly on ADAMTS-4 and iNOS Levels in Osteoarthritis Rat Model. Open access Macedonian journal of medical sciences 5 31110568
2013 Transcript levels of major MMPs and ADAMTS-4 in relation to the clinicopathological profile of patients with tuberculous intervertebral discs and healthy controls. Clinical biochemistry 5 23481488
2024 miR-126a-5p inhibits H1N1-induced inflammation and matrix protease secretion in lung fibroblasts by targeting ADAMTS-4. Archives of virology 4 38990242
2020 Purification and Activity Determination of ADAMTS-4 and ADAMTS-5 and Their Domain Deleted Mutants. Methods in molecular biology (Clifton, N.J.) 4 31463904
2014 Matrilin-2 is proteolytically cleaved by ADAMTS-4 and ADAMTS-5. Molecules (Basel, Switzerland) 4 24959676
2008 Conserved sequence in the aggrecan interglobular domain modulates cleavage by ADAMTS-4 and ADAMTS-5. Biochimica et biophysica acta 4 19101611
2025 LncRNA MSTRG.14227.1 regulates the morphogenesis of secondary hair follicles in Inner Mongolia cashmere goats via targeting ADAMTS3 by sponging chi-miR-433. Journal of animal science 3 39715333
2021 β-Ecdysone attenuates cartilage damage in a mouse model of collagenase-induced osteoarthritis via mediating FOXO1/ADAMTS-4/5 signaling axis. Histology and histopathology 3 33876419
2020 Expression and Preparation of Recombinant Reelin and ADAMTS-3 Proteins. Methods in molecular biology (Clifton, N.J.) 3 31463905
2024 Sesame oil downregulates the expression of ADAMTS-4 in high-fat diet-induced atherosclerosis. Prostaglandins & other lipid mediators 2 38936541
2024 Chrysin downregulates the expression of ADAMTS-4 in foam cells. Molecular biology reports 2 39249599
2023 Oxidized LDL-mediated upregulation of ADAMTS-4 in monocytes/macrophages involves ROS-NF-κB-SIRT-1 pathway. Physiology international 2 37216221
2025 The Relationship Between ADAMTS-4 and ADAMTS-5 Enzyme Levels in Patients With Degenerative Disc Disease: A Prospective Biochemical Study. JOR spine 1 39781089
2023 ADAMTS3 and FLT4 gene mutations result in congenital lymphangiectasia in newborns: A case report. World journal of clinical cases 1 37583869
2021 [USF1 Suppresses Expression of Fibrillar Type I, II, and III Collagen and pNP Adamts-3 in Osteosarcoma Cells]. Molekuliarnaia biologiia 1 34432781
2019 [Electroacupuncture down-regulates expression of ADAMTS-4 of intervertebral disc in rats with lumbar intervertebral disc degeneration]. Zhen ci yan jiu = Acupuncture research 1 31056878
2026 Integrative genomic and functional characterization of ADAMTS3 reveals its inflammatory regulation via NF-κB and STAT3 pathways in osteosarcoma. Journal of cell communication and signaling 0 42083632
2026 Hypoxia reprograms VEGF signaling to differentially control ADAMTS2 and ADAMTS3 expression in endothelial cells. Tissue & cell 0 42224870
2024 A Splice Site Variant in ADAMTS3 Is the Likely Causal Variant for Pulmonary Hypoplasia with Anasarca in Persian/Persian-Cross Sheep. Animals : an open access journal from MDPI 0 39409761

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