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Coculture of bovine cartilage with synovium and fibrous joint capsule increases aggrecanase and matrix metalloproteinase activity

Swärd, Per LU ; Wang, Yang; Hansson, Maria; Lohmander, L. Stefan LU ; Grodzinsky, Alan J. LU and Struglics, André LU (2017) In Arthritis Research and Therapy 19(1).
Abstract

Background: A hallmark of osteoarthritis is increased proteolytic cleavage of aggrecan. Cross talk between cartilage and the synovium + joint capsule (SJC) can drive cartilage degradation by activating proteases in both tissues. We investigated aggrecan proteolysis patterns in cartilage explants using a physiologically relevant explant model of joint injury combining cartilage mechanical compression and coincubation with SJC. Methods: Bovine cartilage explants were untreated; coincubated with SJC; or subjected to mechanical injury and coincubated with SJC, mechanical injury alone, or mechanical injury and incubated with tumor necrosis factor-α (TNF-α). To compare the patterns of aggrecan proteolysis between 6 h and 16 days, release of... (More)

Background: A hallmark of osteoarthritis is increased proteolytic cleavage of aggrecan. Cross talk between cartilage and the synovium + joint capsule (SJC) can drive cartilage degradation by activating proteases in both tissues. We investigated aggrecan proteolysis patterns in cartilage explants using a physiologically relevant explant model of joint injury combining cartilage mechanical compression and coincubation with SJC. Methods: Bovine cartilage explants were untreated; coincubated with SJC; or subjected to mechanical injury and coincubated with SJC, mechanical injury alone, or mechanical injury and incubated with tumor necrosis factor-α (TNF-α). To compare the patterns of aggrecan proteolysis between 6 h and 16 days, release of sulfated glycosaminoglycans and specific proteolytic aggrecan fragments into medium or remaining in cartilage explants was measured by dimethylmethylene blue and Western blot analysis. Results: Aggrecanase activity toward aggrecan was observed in all conditions, but it was directed toward the TEGE↓ARGS interglobular domain (IGD) site only when cartilage was coincubated with SJC or TNF-α. Matrix metalloproteinase (MMP) activity at the aggrecan IGD site (IPES↓FFGV) was not detected when cartilage was exposed to TNF-α (up to 6 days), but it was in all other conditions. Compared with when bovine cartilage was left untreated or subjected to mechanical injury alone, additional aggrecan fragment types were released into medium and proteolysis of aggrecan started at an earlier time when SJC was present. Conclusions: Indicative of different proteolytic pathways for aggrecan degradation, the SJC increases both aggrecanase and MMP activity toward aggrecan, whereas TNF-α inhibits MMP activity against the IGD of aggrecan.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aggrecan, Aggrecanases, Cartilage injury, Fibrous joint capsule, Knee injury, Metalloproteinases, Synovium
in
Arthritis Research and Therapy
volume
19
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85021717597
  • wos:000404801100001
ISSN
1478-6354
DOI
10.1186/s13075-017-1318-9
language
English
LU publication?
yes
id
5b121234-6251-4107-b9df-d46e1123f189
date added to LUP
2017-07-26 10:29:25
date last changed
2017-09-18 11:39:39
@article{5b121234-6251-4107-b9df-d46e1123f189,
  abstract     = {<p>Background: A hallmark of osteoarthritis is increased proteolytic cleavage of aggrecan. Cross talk between cartilage and the synovium + joint capsule (SJC) can drive cartilage degradation by activating proteases in both tissues. We investigated aggrecan proteolysis patterns in cartilage explants using a physiologically relevant explant model of joint injury combining cartilage mechanical compression and coincubation with SJC. Methods: Bovine cartilage explants were untreated; coincubated with SJC; or subjected to mechanical injury and coincubated with SJC, mechanical injury alone, or mechanical injury and incubated with tumor necrosis factor-α (TNF-α). To compare the patterns of aggrecan proteolysis between 6 h and 16 days, release of sulfated glycosaminoglycans and specific proteolytic aggrecan fragments into medium or remaining in cartilage explants was measured by dimethylmethylene blue and Western blot analysis. Results: Aggrecanase activity toward aggrecan was observed in all conditions, but it was directed toward the TEGE↓ARGS interglobular domain (IGD) site only when cartilage was coincubated with SJC or TNF-α. Matrix metalloproteinase (MMP) activity at the aggrecan IGD site (IPES↓FFGV) was not detected when cartilage was exposed to TNF-α (up to 6 days), but it was in all other conditions. Compared with when bovine cartilage was left untreated or subjected to mechanical injury alone, additional aggrecan fragment types were released into medium and proteolysis of aggrecan started at an earlier time when SJC was present. Conclusions: Indicative of different proteolytic pathways for aggrecan degradation, the SJC increases both aggrecanase and MMP activity toward aggrecan, whereas TNF-α inhibits MMP activity against the IGD of aggrecan.</p>},
  articleno    = {157},
  author       = {Swärd, Per and Wang, Yang and Hansson, Maria and Lohmander, L. Stefan and Grodzinsky, Alan J. and Struglics, André},
  issn         = {1478-6354},
  keyword      = {Aggrecan,Aggrecanases,Cartilage injury,Fibrous joint capsule,Knee injury,Metalloproteinases,Synovium},
  language     = {eng},
  month        = {07},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Coculture of bovine cartilage with synovium and fibrous joint capsule increases aggrecanase and matrix metalloproteinase activity},
  url          = {http://dx.doi.org/10.1186/s13075-017-1318-9},
  volume       = {19},
  year         = {2017},
}