Abstract | OBJECTIVE: To identify and characterize a cartilage degradation mechanism that is independent of the proteolytic cleavages by matrix metalloproteinases ( MMPs) and aggrecanases. METHODS: RESULTS:
AG3340 did not effectively inhibit GAG release at a concentration of more than 10muM, while 10nM of the inhibitor completely suppressed collagen degradation. Retinoic acid induced the release of the aggrecan G1 domain, link protein and HA into the culture medium, and the release of these molecules was not completely inhibited by 10muM of AG3340. The molecules were released as ternary complexes. Retinoic acid induced HA degradation in the explant culture and hyaluronidase activity in the primary culture of chondrocytes. The release of the G1 domain of aggrecan and link protein into the synovial fluid was also observed in the IL-1alpha-induced acute arthritis model. CONCLUSION: A novel mechanism by chondrocyte-derived hyaluronidase(s) is involved in the release of the matrix components from cartilage, and the hyaluronidase(s) and MMPs/aggrecanases act in a coordinated manner in cartilage degradation.
|
Authors | Kotaro Sugimoto, Tomoko Iizawa, Hosami Harada, Kazuyo Yamada, Mutsumi Katsumata, Masaaki Takahashi |
Journal | Osteoarthritis and cartilage
(Osteoarthritis Cartilage)
Vol. 12
Issue 12
Pg. 1006-14
(Dec 2004)
ISSN: 1063-4584 [Print] England |
PMID | 15564068
(Publication Type: Journal Article)
|
Chemical References |
- Aggrecans
- Collagen Type II
- Extracellular Matrix Proteins
- Glycosaminoglycans
- Interleukin-1
- Lectins, C-Type
- Matrix Metalloproteinase Inhibitors
- Organic Chemicals
- Peptides
- Proteoglycans
- Oncostatin M
- prinomastat
- Tretinoin
- Endopeptidases
- aggrecanase
|
Topics |
- Aggrecans
- Animals
- Cartilage
(drug effects, metabolism, pathology)
- Cattle
- Collagen Type II
(metabolism)
- Endopeptidases
(metabolism)
- Extracellular Matrix Proteins
(metabolism)
- Glycosaminoglycans
(metabolism)
- Interleukin-1
(pharmacology)
- Lectins, C-Type
- Matrix Metalloproteinase Inhibitors
- Oncostatin M
- Organic Chemicals
(pharmacology)
- Peptides
(pharmacology)
- Proteoglycans
(metabolism)
- Rabbits
- Stimulation, Chemical
- Synovial Fluid
(chemistry)
- Tissue Culture Techniques
- Tretinoin
(pharmacology)
|