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ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury

Demircan, K, Topcu, V, Takigawa, T, Akyol, S, Yonezawa, T, Ozturk, G, Ugurcu, V, Hasgul, R, Yigitoglu, M R, Akyol, O, McCulloch, D R and Hirohata, S 2014, ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury, Biomed Research International, vol. 2014, Article number 693746, pp. 1-8, doi: 10.1155/2014/693746.

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Title ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury
Author(s) Demircan, K
Topcu, V
Takigawa, T
Akyol, S
Yonezawa, T
Ozturk, G
Ugurcu, V
Hasgul, R
Yigitoglu, M R
Akyol, O
McCulloch, D R
Hirohata, S
Journal name Biomed Research International
Volume number 2014
Season Article number 693746
Start page 1
End page 8
Total pages 8
Publisher Hindawi
Place of publication New York, NY
Publication date 2014
ISSN 2314-6141
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Biotechnology & Applied Microbiology
Medicine, Research & Experimental
Research & Experimental Medicine
HUMAN ARTICULAR-CARTILAGE
THROMBOSPONDIN MOTIFS
EXTRACELLULAR-MATRIX
DEFICIENT MICE
METALLOPROTEINASE
MOUSE
DISINTEGRIN
CLEAVAGE
PROTEOGLYCAN
DEGRADATION
Summary 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 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.
Language eng
DOI 10.1155/2014/693746
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Biomed Central
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30067858

Document type: Journal Article
Collections: School of Medicine
Open Access Collection
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Created: Mon, 08 Dec 2014, 14:29:11 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.