{"doi":"10.1155/2014/693746","title":"ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury","abstract":"<jats:p>The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for<jats:italic>Adamts4</jats:italic>or<jats:italic>Adamts5</jats:italic>null alleles after spinal cord injury (SCI). ADAMTS-derived 50–60 kDa aggrecan and 50 kDa brevican fragments were observed in<jats:italic>Adamts4−/−</jats:italic>,<jats:italic>Adamts5−/−</jats:italic>, and<jats:italic>wt</jats:italic>mice but not in the sham-operated group. By contrast<jats:italic>Adamts4−/−</jats:italic>and<jats:italic>Adamts5−/−</jats:italic>mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in<jats:italic>Adamts4−/−</jats:italic>mice’ spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in<jats:italic>Adamts4−/−</jats:italic>or<jats:italic>Adamts5−/−</jats:italic>mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.</jats:p>","journal":"BioMed Research International","year":2014,"id":687062,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1794936,"name":"Vehap Topcu","orcid":null,"position":1,"is_corresponding":false},{"id":1794937,"name":"Tomoyuki Takigawa","orcid":null,"position":2,"is_corresponding":false},{"id":1590905,"name":"Sumeyya Akyol","orcid":null,"position":3,"is_corresponding":false},{"id":1794938,"name":"Tomoko Yonezawa","orcid":null,"position":4,"is_corresponding":false},{"id":1794939,"name":"Gulfer Ozturk","orcid":null,"position":5,"is_corresponding":false},{"id":1794940,"name":"Veli Ugurcu","orcid":null,"position":6,"is_corresponding":false},{"id":1794941,"name":"Rukiye Hasgul","orcid":null,"position":7,"is_corresponding":false},{"id":1794942,"name":"M. Ramazan Yigitoglu","orcid":null,"position":8,"is_corresponding":false},{"id":1727251,"name":"Omer Akyol","orcid":"0000-0001-5496-9392","position":9,"is_corresponding":false},{"id":1794943,"name":"Daniel R. McCulloch","orcid":null,"position":10,"is_corresponding":false},{"id":1711066,"name":"Satoshi Hirohata","orcid":null,"position":11,"is_corresponding":false},{"id":1711068,"name":"Kadir Demircan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury","abstract":"<jats:p>The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for<jats:italic>Adamts4</jats:italic>or<jats:italic>Adamts5</jats:italic>null alleles after spinal cord injury (SCI). ADAMTS-derived 50–60 kDa aggrecan and 50 kDa brevican fragments were observed in<jats:italic>Adamts4−/−</jats:italic>,<jats:italic>Adamts5−/−</jats:italic>, and<jats:italic>wt</jats:italic>mice but not in the sham-operated group. By contrast<jats:italic>Adamts4−/−</jats:italic>and<jats:italic>Adamts5−/−</jats:italic>mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in<jats:italic>Adamts4−/−</jats:italic>mice’ spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in<jats:italic>Adamts4−/−</jats:italic>or<jats:italic>Adamts5−/−</jats:italic>mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.</jats:p>","is_dataset_classified":null,"base_score":3.713572066704308,"endowment":3.713572066704308,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25101296","pmcid":"PMC4101972","openalex_id":"https://openalex.org/W2157439776","authors":[],"funders":[{"funder_name":"Japan Society for the Promotion of Science","grant_id":"","title":null},{"funder_name":"Financial Markets Foundation for Children","grant_id":"","title":null},{"funder_name":"Technological Research Council of Turkey","grant_id":"","title":null},{"funder_name":"Arthritis Foundation","grant_id":"","title":null}],"total_grants":4,"fwci":1.8265,"citation_percentile":0.83948187,"influential_citations":0,"citation_trend":[{"year":2015,"count":4},{"year":2016,"count":3},{"year":2017,"count":6},{"year":2018,"count":1},{"year":2019,"count":3},{"year":2020,"count":5},{"year":2021,"count":3},{"year":2022,"count":4},{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://downloads.hindawi.com/journals/bmri/2014/693746.pdf","host_type":"journal"},{"url":"https://downloads.hindawi.com/journals/bmri/2014/693746.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/bmri/2014/693746.pdf","host_type":"publisher"},{"url":"http://downloads.hindawi.com/journals/bmri/2014/693746.xml","host_type":"publisher"},{"url":"https://doi.org/10.1155/2014/693746","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25101296","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4101972","host_type":"repository"},{"url":"https://doaj.org/article/ab9adfcee8b7448dbed266eee874dda5","host_type":"repository"},{"url":"http://www.doi.org/10.1155/2014/693746","host_type":"repository"},{"url":"https://figshare.com/articles/journal_contribution/ADAMTS4_and_ADAMTS5_knockout_mice_are_protected_from_versican_but_not_aggrecan_or_brevican_proteolysis_during_spinal_cord_injury/20928202","host_type":"repository"},{"url":"http://hdl.handle.net/11655/16293","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4101972","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4101972?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Proteoglycans and glycosaminoglycans research","Osteoarthritis Treatment and Mechanisms","Protease and Inhibitor Mechanisms","ADAM Proteins","ADAMTS4 Protein","ADAMTS5 Protein","Aggrecans","Animals","Axons","Brevican","Humans","Mice","Mice, Knockout","Procollagen N-Endopeptidase","Proteolysis","Spinal Cord Injuries","Versicans"],"mesh_terms":["ADAMTS5 Protein","ADAMTS4 Protein","Animals","Axons","Humans","Procollagen N-Endopeptidase","Spinal Cord Injuries","Mice, Knockout","Mice","ADAM Proteins","Aggrecans","Versicans","Brevican","Proteolysis"],"keywords":["Versican","ADAMTS","Aggrecan","Chemistry","Proteolysis","Proteoglycan","Cell biology","Perineuronal net","Spinal cord injury","Molecular biology","Spinal cord","Extracellular matrix","Biology","Biochemistry","Pathology","Metalloproteinase","Medicine","Matrix metalloproteinase","Thrombospondin","Neuroscience"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T21:13:43.015661Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}