Document Detail


Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage.
MedLine Citation:
PMID:  19747586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Osteoarthritis is a disease process of cellular degradation of articular cartilage caused by mechanical loads and inflammatory cytokines. We studied the cellular response in native cartilage subjected to a mechanical load administered simultaneously with an inflammatory cytokine interleukin-1 (IL-1), hypothesizing that the combination of load and cytokine would result in accelerated extracellular matrix (ECM) degradation.
METHODS: Mature bovine articular cartilage was loaded for 3 days (stimulation) with 0.2 and 0.5 MPa stresses, with and without IL-1 (IL-1alpha, 10 ng/ml), followed by 3 days of no stimulation (recovery). Aggrecan and collagen loss were measured as well as aggrecan cleavage using monoclonal antibodies AF-28 and BC-3 for cleavage by aggrecanases (ADAMTS) and matrix metalloproteinases (MMPs), respectively.
RESULTS: Incubation with IL-1 caused aggrecan cleavage by aggrecanases and MMPs during the 3 days of stimulation. A load of 0.5 MPa inhibited the IL-1-induced aggrecan loss while no inhibition was found for the 0.2 MPa stress. There was no collagen loss during the treatments but upon load and IL-1 removal proteoglycan and collagen loss increased. Load itself under these conditions was found to have no effect when compared to the unloaded controls.
CONCLUSIONS: A mechanical load of sufficient magnitude can inhibit ECM degradation by chondrocytes when stimulated by IL-1. The molecular mechanisms involved in this process are not clear but probably involve altered mechanochemical signal transduction between the ECM and chondrocyte.
Authors:
P A Torzilli; M Bhargava; S Park; C T C Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-09-01
Journal Detail:
Title:  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society     Volume:  18     ISSN:  1522-9653     ISO Abbreviation:  Osteoarthr. Cartil.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-05-11     Revised Date:  2011-07-19    
Medline Journal Info:
Nlm Unique ID:  9305697     Medline TA:  Osteoarthritis Cartilage     Country:  England    
Other Details:
Languages:  eng     Pagination:  97-105     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York, NY 10021-4010, USA. torzillip@hss.edu
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MeSH Terms
Descriptor/Qualifier:
Aggrecans / metabolism*
Animals
Antibodies, Monoclonal / immunology
Cartilage, Articular / drug effects,  enzymology,  physiology*
Cattle
Collagen / metabolism*
Endopeptidases / immunology,  metabolism
Interleukin-1 / pharmacology*
Matrix Metalloproteinases / immunology,  metabolism
Stress, Mechanical
Grant Support
ID/Acronym/Agency:
AR45748/AR/NIAMS NIH HHS; C06-RR12538-01/RR/NCRR NIH HHS; R01 AR045748-09/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Aggrecans; 0/Antibodies, Monoclonal; 0/Interleukin-1; 9007-34-5/Collagen; EC 3.4.-/Endopeptidases; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.4.99.-/aggrecanase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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