Affinage

ADAMTS3

A disintegrin and metalloproteinase with thrombospondin motifs 3 · UniProt O15072

Round 2 corrected
Length
1205 aa
Mass
135.6 kDa
Annotated
2026-04-28
126 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAMTS3 is a secreted zinc metalloproteinase with multiple physiologically important substrates, functioning in collagen maturation, lymphangiogenesis, neuronal Reelin signaling, and extracellular matrix remodeling. It cleaves the N-propeptide of procollagen II and is the predominant procollagen II N-propeptidase in cartilage (PMID:11408482); it proteolytically activates pro-VEGFC in cooperation with CCBE1, a step essential for VEGFC/VEGFR3-driven lymphangiogenesis, and bi-allelic loss-of-function mutations cause Hennekam lymphangiectasia-lymphedema syndrome 3 (PMID:28985353, PMID:35316211). In the brain, ADAMTS3 is the principal protease that cleaves and inactivates Reelin at the N-t site, thereby modulating dendritic morphogenesis and amyloid-β deposition (PMID:28213441, PMID:30828067). ADAMTS3 also degrades fibronectin in the breast tumor microenvironment, restraining integrin α5β1-mediated invasion (PMID:37336268).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2001 Medium

    Molecular cloning established ADAMTS3 as a new member of the ADAMTS zinc metalloproteinase family with a characteristic multi-domain architecture, addressing the question of gene identity and domain organization.

    Evidence cDNA cloning, domain analysis, and Northern blot/in situ hybridization during mouse embryogenesis

    PMID:10464288

    Open questions at the time
    • No enzymatic activity demonstrated at this stage
    • Physiological substrates unknown
  2. 2001 High

    A functional rescue experiment showed that ADAMTS3 possesses procollagen II N-propeptidase activity and is the likely dominant enzyme for this function in cartilage, answering whether ADAMTS family members beyond ADAMTS2 could process procollagen II.

    Evidence Stable transfection of ADAMTS3 into RCS-LTC cells rescued procollagen II N-propeptide processing; RT-PCR showed 5-fold higher ADAMTS3 than ADAMTS2 mRNA in human cartilage

    PMID:11408482

    Open questions at the time
    • No in vivo knockout confirmation of cartilage phenotype
    • Relative contribution versus ADAMTS2 and ADAMTS14 not resolved
  3. 2017 High

    Identification of ADAMTS3 as the principal Reelin-cleaving enzyme in the cerebral cortex resolved a long-standing question about how Reelin signaling is terminated, revealing roles in dendritic morphogenesis and cortical development.

    Evidence Purification of Reelin-cleaving activity from cortical neuron supernatants; recombinant ADAMTS3 cleavage assay; global and conditional ADAMTS3 KO mice with biochemical (Dab1, Tau phosphorylation) and morphological (dendritic branching) readouts

    PMID:28213441

    Open questions at the time
    • Whether other ADAMTS proteases contribute to Reelin cleavage in vivo
    • Mechanism of ADAMTS3 regulation in neurons not defined
  4. 2017 High

    Human genetic evidence demonstrated that ADAMTS3 is the essential activator of pro-VEGFC for lymphangiogenesis, placing it in the CCBE1–ADAMTS3–VEGFC–VEGFR3 signaling axis and establishing a Mendelian disease mechanism.

    Evidence Whole-exome sequencing identified bi-allelic ADAMTS3 mutations in Hennekam syndrome patients; in vitro expression showed mutant proteins were retained intracellularly and failed to activate pro-VEGFC

    PMID:28985353

    Open questions at the time
    • Structural basis of CCBE1–ADAMTS3 cooperation unresolved
    • Whether residual pro-VEGFC activation occurs through ADAMTS2/14 in these patients
  5. 2019 Medium

    Linking ADAMTS3-mediated Reelin inactivation to amyloid-β pathology showed that reducing ADAMTS3 protects against Aβ deposition in a wild-type Aβ model, extending the enzyme's relevance to neurodegeneration.

    Evidence Drug-inducible conditional ADAMTS3 KO crossed with AppNL-F and AppNL-G-F knock-in mice; quantification of Aβ deposits

    PMID:30828067

    Open questions at the time
    • Mechanism linking enhanced Reelin signaling to reduced Aβ deposition not dissected
    • Effect limited to wild-type Aβ; no benefit with Arctic mutant Aβ
    • Single study, not independently replicated
  6. 2022 High

    Demonstration that ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in pro-VEGFC activation in adults clarified redundancy within the ADAMTS procollagen N-propeptidase subclade for lymphangiogenesis.

    Evidence Recombinant in vitro cleavage assays; Adamts2-KO mice with skin lymphedema; Adamts2/Adamts14 double-KO corneal lymphangiogenesis model

    PMID:35316211

    Open questions at the time
    • Relative contributions of ADAMTS3 versus ADAMTS2/14 during embryonic versus adult lymphangiogenesis not fully delineated
    • No triple-KO model
  7. 2023 Medium

    Identification of fibronectin as a novel ADAMTS3 substrate revealed a tumor-suppressive role in breast cancer, showing that myoepithelial ADAMTS3 limits invasion by preventing fibronectin-driven integrin α5β1 activation.

    Evidence TAILS degradomics; heterocellular spheroid invasion assays; integrin-blocking experiments

    PMID:37336268

    Open questions at the time
    • In vivo validation of tumor-suppressive role lacking
    • Whether fibronectin degradation is relevant outside breast cancer not tested
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the structural basis of CCBE1-dependent ADAMTS3 activation of pro-VEGFC, whether ADAMTS3 has additional physiological substrates, the regulation of ADAMTS3 activity in the brain, and the in vivo significance of fibronectin cleavage in cancer.
  • No crystal structure or cryo-EM model of ADAMTS3 or ADAMTS3–CCBE1 complex
  • Full substrate repertoire not systematically mapped
  • Transcriptional and post-translational regulation largely unexplored beyond USF1

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 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-162582 Signal Transduction 2
Partners
CCBE1FN1RELNVEGFC

Evidence

Reading pass · 10 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 ADAMTS-3 into RCS-LTC cells (which fail to process procollagen II N-propeptide) partially rescued the processing defect, demonstrating that ADAMTS-3 can cleave the procollagen II N-propeptide. ADAMTS-3 mRNA is expressed 5-fold higher than ADAMTS-2 in human cartilage, suggesting it is the physiologically more relevant procollagen II N-propeptidase in cartilage. Stable transfection rescue assay in RCS-LTC cells; RT-PCR mRNA expression analysis in human tissues The Journal of biological chemistry High 11408482
2017 ADAMTS-3 is the major enzyme 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 of Reelin was markedly decreased in the embryonic cerebral cortex of ADAMTS-3 knock-out mice. ADAMTS-3 KO mice showed decreased Dab1 levels and decreased Tau phosphorylation (indicative of increased Reelin signaling), and conditional KO of ADAMTS-3 in excitatory neurons increased dendritic branching and elongation in the postnatal cerebral cortex. Partial purification and identification of the Reelin-cleaving enzyme from cortical neuron supernatant; recombinant ADAMTS-3 in vitro cleavage assay; ADAMTS-3 knock-out mice with biochemical and morphological readouts; conditional KO in excitatory neurons The Journal of neuroscience High 28213441
2017 Loss-of-function mutations in ADAMTS3 cause Hennekam lymphangiectasia-lymphedema syndrome 3 (HKLLS3). Bi-allelic missense mutations affecting conserved residues in the prodomain and peptidase domain of ADAMTS3 result in abnormal processing and intracellular sequestration of the mutant proteins, abolishing proteolytic activation of pro-VEGFC. This places ADAMTS3 as a key activator of the VEGFC/VEGFR3 lymphangiogenic signaling axis, functionally interacting with CCBE1. Whole-exome sequencing; in vitro expression and processing assays of mutant proteins; pro-VEGFC activation assay Human molecular genetics High 28985353
2019 Reducing ADAMTS-3 inhibits amyloid β (Aβ) deposition in AppNL-F knock-in mice (which produce human wild-type Aβ), consistent with ADAMTS-3-mediated Reelin inactivation promoting Aβ accumulation. No effect was observed in AppNL-G-F mice producing the Arctic mutant Aβ, suggesting the protective mechanism is specific to wild-type Aβ pathology. Drug-inducible conditional ADAMTS-3 knock-out mice crossed with next-generation AD model mice; Aβ deposition quantification Biological & pharmaceutical bulletin Medium 30828067
2022 ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in processing pro-VEGFC into active VEGFC in adults. In vitro, both cleave pro-VEGFC as efficiently as ADAMTS3. In vivo, adult Adamts2-KO mice develop skin lymphedema due to reduced lymphatic vessel density/diameter, while Adamts14-KO had no phenotype alone but combined Adamts2/Adamts14 double-KO further reduced lymphangiogenesis in a corneal injury model. In vitro pro-VEGFC processing assays with recombinant proteins; Adamts2-KO, Adamts14-KO, and double-KO mice; lymphatic vessel imaging; corneal lymphangiogenesis model JCI insight High 35316211
2019 A missense variant (c.2786G>A) in ADAMTS3 is associated with Upper Airway Syndrome in Norwich Terriers and enriched in BOAS-susceptible French and English Bulldogs, suggesting that disruption of ADAMTS3 function causes airway oedema (consistent with its role in lymphatic development/function) that predisposes to respiratory obstruction. Genome-wide association analysis; whole genome resequencing; Sanger sequencing; genotyping in 401 dogs PLoS genetics Medium 31095560
2023 ADAMTS3 acts as a tumour suppressor in early breast cancer by mediating fibronectin degradation. Loss of myoepithelial ADAMTS3 enhances fibronectin levels in the microenvironment, promoting invasion through canonical integrin α5β1 activation. Degradomic analysis (TAILS) identified fibronectin as an ADAMTS3 substrate. Heterocellular spheroid invasion model; TAILS degradomics; functional invasion assays; integrin α5β1 blocking experiments Matrix biology Medium 37336268
2021 USF1 transcription factor negatively regulates ADAMTS-3 expression: overexpression of USF1 in osteosarcoma cells decreased ADAMTS-3 mRNA and protein levels, suppressed ADAMTS-3 promoter activity in co-transfection studies, and USF1 binding to the ADAMTS-3 promoter region was confirmed by EMSA. Ectopic USF1 overexpression; co-transfection promoter-reporter assays; EMSA Molekuliarnaia biologiia Medium 34432781
2024 A splice site variant in ADAMTS3 (single nucleotide deletion 3 bp downstream from a donor splice site in exon 14) is the likely causal variant for pulmonary hypoplasia with anasarca (hydrops fetalis) in Persian/Persian-cross sheep, introducing an early splice site and loss of 6 amino acids at the exon14/intron14-15 junction, segregating with disease in 209 animals. SNP genotyping (homozygosity mapping); whole genome sequencing; Sanger sequencing of cDNA; genotyping assay Animals Medium 39409761
2001 ADAMTS3 (then called ADAM-TS3/KIAA0366) was identified as a member of the ADAMTS family of zinc metalloproteinases, characterized by a preproregion, reprolysin-type catalytic domain, disintegrin-like domain, thrombospondin type-1 module, cysteine-rich domain, and spacer domain, with differential expression during mouse embryogenesis. cDNA cloning; domain architecture analysis; Northern blot/in situ expression profiling during embryogenesis The Journal of biological chemistry Medium 10464288

Source papers

Stage 0 corpus · 126 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
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
2004 Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis and rheumatism 334 14730609
2007 Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis and rheumatism 333 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
2001 ADAMTS: a novel family of extracellular matrix proteases. The international journal of biochemistry & cell biology 270 11167130
1999 Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. American journal of human genetics 268 10417273
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2004 Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice. Arthritis and rheumatism 245 15334469
2012 Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS genetics 222 22589738
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 183 11408482
2003 Altered proteolytic activities of ADAMTS-4 expressed by C-terminal processing. The Journal of biological chemistry 175 14662755
1999 ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family. The Journal of biological chemistry 171 10464288
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 163 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 153 11741898
2002 Autocatalytic cleavage of ADAMTS-4 (Aggrecanase-1) reveals multiple glycosaminoglycan-binding sites. The Journal of biological chemistry 123 12202483
2015 The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology. Matrix biology : journal of the International Society for Matrix Biology 118 25863161
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2007 ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of human atherosclerotic plaques. Atherosclerosis 100 17606262
2022 EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation. Nature communications 99 35013218
2004 Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene. The Journal of investigative dermatology 95 15373769
2013 MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes. Arthritis research & therapy 88 23406982
2008 Genome-wide association scan of the time to onset of attention deficit hyperactivity disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 88 18937294
2008 Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. Rheumatology international 88 18941754
2005 Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V. The Journal of biological chemistry 88 16046392
2017 Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3. Human molecular genetics 82 28985353
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 The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury. Journal of neuroinflammation 76 22420304
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 68 23082219
1999 ADAMTS: a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats. FEBS letters 68 10094461
2015 Discovery of Potent and Selective Inhibitors for ADAMTS-4 through DNA-Encoded Library Technology (ELT). ACS medicinal chemistry letters 64 26288689
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 64 25045124
2010 ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity. Cellular and molecular life sciences : CMLS 59 20574651
2017 Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin. The Journal of neuroscience : the official journal of the Society for Neuroscience 58 28213441
2013 Tumor necrosis factor-α induces ADAMTS-4 expression in human osteoarthritis chondrocytes. Molecular medicine reports 57 24126638
2005 ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms. Archives of biochemistry and biophysics 57 16289022
2012 A genome-wide association study identifies a gene network of ADAMTS genes in the predisposition to pediatric stroke. Blood 56 22990015
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
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 56 17470431
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
2008 Protein interaction data set highlighted with human Ras-MAPK/PI3K signaling pathways. Journal of proteome research 39 18624398
2000 ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) is transcriptionally induced in beta-amyloid treated rat astrocytes. Neuroscience letters 38 10961658
2016 Anti-inflammatory effects of ADAMTS-4 in a mouse model of ischemic stroke. Glia 37 27301579
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
2016 Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type. Genetics in medicine : official journal of the American College of Medical Genetics 33 26765342
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
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
2011 Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis. International journal of rheumatic diseases 31 22324945
2007 Substrate-dependent inhibition kinetics of an active site-directed inhibitor of ADAMTS-4 (Aggrecanase 1). Biochemistry 29 17487981
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
2020 MiR-126a-5p limits the formation of abdominal aortic aneurysm in mice and decreases ADAMTS-4 expression. Journal of cellular and molecular medicine 27 32469162
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
2016 ADAMTS-4 promotes neurodegeneration in a mouse model of amyotrophic lateral sclerosis. Molecular neurodegeneration 26 26809777
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
2014 IL-6 upregulates a disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS-2) in human osteosarcoma cells mediated by JNK pathway. Molecular and cellular biochemistry 24 24752352
2019 Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics. Translational psychiatry 23 31740729
2012 Expression of ADAMTS-2, -3, -13, and -14 in culprit coronary lesions in patients with acute myocardial infarction or stable angina. Journal of thrombosis and thrombolysis 22 22205175
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
2018 IL-1β-induced miR-34a up-regulation inhibits Cyr61 to modulate osteoarthritis chondrocyte proliferation through ADAMTS-4. Journal of cellular biochemistry 20 29236314
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
2012 Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines. International journal of oncology 19 22735305
2009 Adaptor proteins and Ras synergistically regulate IL-1-induced ADAMTS-4 expression in human chondrocytes. Journal of immunology (Baltimore, Md. : 1950) 18 19342688
2002 Human thrombospondin 2 inhibits proliferation of microvascular endothelial cells. International journal of oncology 18 11788898
2019 An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome. PLoS genetics 17 31095560
2018 Leptin induces MMP1/13 and ADAMTS 4 expressions through bone morphogenetic protein-2 autocrine effect in human chondrocytes. Journal of cellular biochemistry 17 29236309
2014 Gene expression profiling of craniofacial fibrous dysplasia reveals ADAMTS2 overexpression as a potential marker. International journal of clinical and experimental pathology 16 25674217
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
1995 The natural history of human dermatosparaxis (Ehlers-Danlos syndrome type VIIC). Clinical dysmorphology 16 7735500
2022 ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in adults for pro-VEGFC activation and lymphatic homeostasis. JCI insight 15 35316211
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 13 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) 12 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 7 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
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
2025 The Relationship Between ADAMTS-4 and ADAMTS-5 Enzyme Levels in Patients With Degenerative Disc Disease: A Prospective Biochemical Study. JOR spine 0 39781089
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