MMP proteolysis of the human extracellular matrix protein aggrecan is mainly a process of normal turnover
(2012) In Biochemical Journal 446. p.213-223- Abstract
- Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS I region, and the border between the CS2... (More)
- Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS I region, and the border between the CS2 and the G3 domain, and kinetic studies showed a specific order of digestion where the cleavage between CS2 and the G3 domain was the most preferred. In vivo studies showed that OA cartilage contained (per dry weight) 3.4-fold more MMP-generated FFGV fragments compared with normal cartilage, and although aggrecanase-generated SF-ARGS concentrations were increased 14-fold in OA and knee-injured patients compared with levels in knee-healthy reference subjects, the SF-FFGV concentrations did not notably change. The results of the present study suggest that MMPs are mainly involved in normal aggrecan turnover and might have a less-active role in aggrecan degradation during knee injury and OA. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3187992
- author
- Struglics, André LU and Björklund, Maria LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- aggrecan, cartilage, degradation, matrix metalloproteinase, proteolysis, synovial fluid
- in
- Biochemical Journal
- volume
- 446
- pages
- 213 - 223
- publisher
- Portland Press
- external identifiers
-
- wos:000308767500005
- scopus:84865165620
- ISSN
- 0264-6021
- DOI
- 10.1042/BJ20120274
- language
- English
- LU publication?
- yes
- id
- dc589088-7d76-4f2e-a49e-96efd1a9cbc7 (old id 3187992)
- date added to LUP
- 2016-04-01 13:34:25
- date last changed
- 2022-04-21 22:20:32
@article{dc589088-7d76-4f2e-a49e-96efd1a9cbc7, abstract = {{Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS I region, and the border between the CS2 and the G3 domain, and kinetic studies showed a specific order of digestion where the cleavage between CS2 and the G3 domain was the most preferred. In vivo studies showed that OA cartilage contained (per dry weight) 3.4-fold more MMP-generated FFGV fragments compared with normal cartilage, and although aggrecanase-generated SF-ARGS concentrations were increased 14-fold in OA and knee-injured patients compared with levels in knee-healthy reference subjects, the SF-FFGV concentrations did not notably change. The results of the present study suggest that MMPs are mainly involved in normal aggrecan turnover and might have a less-active role in aggrecan degradation during knee injury and OA.}}, author = {{Struglics, André and Björklund, Maria}}, issn = {{0264-6021}}, keywords = {{aggrecan; cartilage; degradation; matrix metalloproteinase; proteolysis; synovial fluid}}, language = {{eng}}, pages = {{213--223}}, publisher = {{Portland Press}}, series = {{Biochemical Journal}}, title = {{MMP proteolysis of the human extracellular matrix protein aggrecan is mainly a process of normal turnover}}, url = {{http://dx.doi.org/10.1042/BJ20120274}}, doi = {{10.1042/BJ20120274}}, volume = {{446}}, year = {{2012}}, }