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.
(Less)
- author
- Swärd, Per
LU
; Wang, Yang
; Hansson, Maria
; Lohmander, L. Stefan
LU
; Grodzinsky, Alan J.
LU
and Struglics, André
LU
- organization
- publishing date
- 2017-07-05
- 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
- article number
- 157
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:28679445
- wos:000404801100001
- scopus:85021717597
- 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
- 2024-05-12 18:02:41
@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>}},
author = {{Swärd, Per and Wang, Yang and Hansson, Maria and Lohmander, L. Stefan and Grodzinsky, Alan J. and Struglics, André}},
issn = {{1478-6354}},
keywords = {{Aggrecan; Aggrecanases; Cartilage injury; Fibrous joint capsule; Knee injury; Metalloproteinases; Synovium}},
language = {{eng}},
month = {{07}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
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}},
doi = {{10.1186/s13075-017-1318-9}},
volume = {{19}},
year = {{2017}},
}