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

Kadir Demircan, Vehap Topcu, Tomoyuki Takigawa, Sumeyya Akyol, Tomoko Yonezawa, Gulfer Ozturk, Veli Ugurcu, Rukiye Hasgul, M. Ramazan Yigitoglu, Omer Akyol, Daniel R. McCulloch, Satoshi Hirohata

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number693746
JournalBioMed Research International
Volume2014
DOIs
Publication statusPublished - 2014

Fingerprint

Brevican
Versicans
Proteolysis
Aggrecans
Chondroitin Sulfate Proteoglycans
Spinal Cord Injuries
Knockout Mice
Neurology
Central Nervous System
Nervous System Trauma
Growth
Astrocytes
Extracellular Matrix
Spinal Cord
Western Blotting
Immunohistochemistry
Alleles
Molecules
Wounds and Injuries

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury. / Demircan, Kadir; Topcu, Vehap; Takigawa, Tomoyuki; Akyol, Sumeyya; Yonezawa, Tomoko; Ozturk, Gulfer; Ugurcu, Veli; Hasgul, Rukiye; Yigitoglu, M. Ramazan; Akyol, Omer; McCulloch, Daniel R.; Hirohata, Satoshi.

In: BioMed Research International, Vol. 2014, 693746, 2014.

Research output: Contribution to journalArticle

Demircan, Kadir ; Topcu, Vehap ; Takigawa, Tomoyuki ; Akyol, Sumeyya ; Yonezawa, Tomoko ; Ozturk, Gulfer ; Ugurcu, Veli ; Hasgul, Rukiye ; Yigitoglu, M. Ramazan ; Akyol, Omer ; McCulloch, Daniel R. ; Hirohata, Satoshi. / ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury. In: BioMed Research International. 2014 ; Vol. 2014.
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AU - Akyol, Sumeyya

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AU - Ozturk, Gulfer

AU - Ugurcu, Veli

AU - Hasgul, Rukiye

AU - Yigitoglu, M. Ramazan

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AU - Hirohata, Satoshi

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AB - 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.

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