| Hyaluronan inhibits matrix metalloproteinase-13 in human arthritic chondrocytes via CD44 and P38. | |
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MedLine Citation:
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PMID: 20706991 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the effects of hyaluronan (HA) on interleukin-1β (IL-1β)-stimulated matrix metalloproteinase (MMP)-13 production in human chondrocytes from patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Secreted levels of MMP-13 in conditioned media were detected by immunoblotting, while intracellular MMP-13 synthesis in articular cartilage was evaluated by immunofluorescence microscopic analysis. Mitogen-activated protein kinases (MAPKs), p38, extracellular signal-regulated kinases (ERK), and c-jun NH2-terminal kinase (JNK) were assessed by Western blotting. IL-1β (2 ng/ml) stimulates the secretion of MMP-13 in both OA and RA chondrocytes. Inhibition studies using specific MAPK inhibitors revealed that IL-1β induced MMP-13 via p38 in both OA and RA chondrocytes. HA down-regulates IL-1β-stimulated MMP-13 and phosphorylated p38 (p-p38) in a dose-dependent manner (0.1, 1, 2, and 4 mg/ml). When used at 4 mg/ml, HA inhibits p-p38 phosphorylation by more than 60%. In response to IL-1β, RA chondrocytes express a higher level of p-p38 than that of OA chondrocytes. Inhibition of CD44, using a blocking antibody, significantly reversed the inhibitory effect of HA on both MMP-13 and p-p38. Our study clearly shows that HA inhibits IL-1β-induced MMP-13 via its principal receptor, CD44, and subsequent intracellular p38 MAPK signaling in OA and RA chondrocytes. |
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Authors:
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Sohel M Julovi; Hiromu Ito; Kohei Nishitani; Christopher J Jackson; Takashi Nakamura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-12 |
Journal Detail:
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Title: Journal of orthopaedic research : official publication of the Orthopaedic Research Society Volume: 29 ISSN: 1554-527X ISO Abbreviation: J. Orthop. Res. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2010-12-24 Completed Date: 2011-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8404726 Medline TA: J Orthop Res Country: United States |
Other Details:
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Languages: eng Pagination: 258-64 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Orthopaedic Research Society. |
Affiliation:
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Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. sjulovi@med.usyd.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD44
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metabolism* Arthritis / drug therapy, enzymology* Cells, Cultured Chondrocytes / drug effects, enzymology Humans Hyaluronic Acid / pharmacology*, therapeutic use Interleukin-1beta Matrix Metalloproteinase 13 / antagonists & inhibitors*, metabolism Viscosupplements / pharmacology, therapeutic use p38 Mitogen-Activated Protein Kinases / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD44; 0/CD44 protein, human; 0/IL1B protein, human; 0/Interleukin-1beta; 0/Viscosupplements; 9004-61-9/Hyaluronic Acid; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.24.-/MMP13 protein, human; EC 3.4.24.-/Matrix Metalloproteinase 13 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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