ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury

Basit Öğe Kaydı
dc.authoridTopcu, Vehap/0000-0001-7224-5697;
dc.contributor.authorDemircan, Kadir
dc.contributor.authorTopcu, Vehap
dc.contributor.authorTakigawa, Tomoyuki
dc.contributor.authorAkyol, Sumeyya
dc.contributor.authorYonezawa, Tomoko
dc.contributor.authorOzturk, Gulfer
dc.contributor.authorUgurcu, Veli
dc.date.accessioned2025-10-24T18:09:26Z
dc.date.available2025-10-24T18:09:26Z
dc.date.issued2014
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractThe 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 Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50-60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4-/-, Adamts5-/-, and wt mice but not in the sham-operated group. By contrast Adamts4-/- and Adamts5-/- 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 Adamts4-/- mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4-/- or Adamts5-/- 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.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK); TUBITAK SBAG [3501]; Japan Society of Promotion Science (JSPS); Takeda Science Foundation Postdoctoral Research; Japan MONBUSHO scholarship; Arthritis Foundation of Australia; Financial Markets Foundation for Children
dc.description.sponsorshipThe authors acknowledge the support of The Scientific and Technological Research Council of Turkey (TUBITAK). Kadir Demircan is funded by the TUBITAK SBAG 3501 Grant. Kadir Demircan also received the Japan Society of Promotion Science (JSPS), Takeda Science Foundation Postdoctoral Research, and Japan MONBUSHO scholarship and grant support, respectively. Daniel McCulloch's laboratory was funded by grants from the Arthritis Foundation of Australia and the Financial Markets Foundation for Children.
dc.identifier.doi10.1155/2014/693746
dc.identifier.issn2314-6133
dc.identifier.issn2314-6141
dc.identifier.scopus2-s2.0-84904801140
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1155/2014/693746
dc.identifier.urihttps://hdl.handle.net/20.500.12899/3650
dc.identifier.volume2014
dc.identifier.wosWOS:000338876600001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherHindawi Ltd
dc.relation.ispartofBiomed Research International
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20251023
dc.subjectThrombospondin Motifs; Extracellular-Matrix; Metalloproteinase; Cartilage; Proteoglycan; Disintegrin; Cleavage; Degradation; Deficient; Fragments
dc.titleADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury
dc.title.alternativeADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury
dc.typeArticle

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu