Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin

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Abstract

Lubricin (PRG4) is a mucin type protein that plays an important role in maintaining normal joint function by providing lubrication and chondroprotection. Improper lubricin modification and degradation has been observed in idiopathic osteoarthritis (OA), while the detailed mechanism still remains unknown. We hypothesized that the protease cathepsin G (CG) may participate in degrading lubricin in synovial fluid (SF). The presence of endogenous CG in SF was confirmed in 16 patients with knee OA. Recombinant human lubricin (rhPRG4) and native lubricin purified from the SF of patients were incubated with exogenous CG and lubricin degradation was monitored using western blot, staining by Coomassie or Periodic Acid-Schiff base in gels, and with proteomics. Full length lubricin (∼300 kDa), was efficiently digested with CG generating a 25-kDa protein fragment, originating from the densely glycosylated mucin domain (∼250 kDa). The 25-kDa fragment was present in the SF from OA patients, and the amount was increased after incubation with CG. A CG digest of rhPRG4 revealed 135 peptides and 72 glycopeptides, and confirmed that the protease could cleave in all domains of lubricin, including the mucin domain. Our results suggest that synovial CG may take part in the degradation of lubricin, which could affect the pathological decrease of the lubrication in degenerative joint disease.

Detaljer

Författare
  • Shan Huang
  • Kristina A. Thomsson
  • Chunsheng Jin
  • Sally Alweddi
  • André Struglics
  • Ola Rolfson
  • Lena I. Björkman
  • Sebastian Kalamajski
  • Tannin A. Schmidt
  • Gregory D. Jay
  • Roman Krawetz
  • Niclas G. Karlsson
  • Thomas Eisler
Enheter & grupper
Externa organisationer
  • Göteborgs universitet
  • Karolinska Institute
  • Sahlgrenska Academy
  • University of Connecticut
  • Brown University
  • University of Calgary
  • Danderyd Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Reumatologi och inflammation
Originalspråkengelska
Artikelnummer4215
TidskriftScientific Reports
Volym10
StatusPublished - 2020 mar 6
PublikationskategoriForskning
Peer review utfördJa