Abstract | OBJECTIVE: METHODS: In vitro, human articular cartilage extract was incubated with activated human recombinant cathepsins (Cats) and matrix- metalloproteases ( MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage sections were then incubated for up to 84 h in the presence or absence of E-64 and GM6001, inhibitors of cysteine proteases and MMPs, respectively. RESULTS: In vitro, Cats K, L and S generated large amount of Helix-II, but not CTX-II. Cat B generated CTX-II fragment, but destroyed Helix-II immunoreactivity. Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA cartilage explants, E-64 blunted the release of Helix-II whereas the release of CTX-II could be completely abrogated by GM6001 and only partly by E-64. CONCLUSION: These in vitro and ex vivo experiments of human cartilage suggest that Helix-II and CTX-II could be released in part by different enzymatic pathways. Helix-II and CTX-II alone reflect only partially overall cartilage collagen degradation. These findings may explain why these two biological markers could provide complementary information on disease progression in OA.
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Authors | N Charni-Ben Tabassi, S Desmarais, A-C Bay-Jensen, J M Delaissé, M D Percival, P Garnero |
Journal | Osteoarthritis and cartilage
(Osteoarthritis Cartilage)
Vol. 16
Issue 10
Pg. 1183-91
(Oct 2008)
ISSN: 1522-9653 [Electronic] England |
PMID | 18403221
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers
- Collagen Type II
- Cathepsins
- Matrix Metalloproteinases
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Topics |
- Biomarkers
(metabolism)
- Cartilage, Articular
(pathology)
- Cathepsins
(metabolism)
- Collagen Type II
(metabolism)
- Humans
- Matrix Metalloproteinases
(metabolism)
- Osteoarthritis, Knee
(pathology)
- Predictive Value of Tests
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