Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage.
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.
Torzilli
P A
PA
Laboratory for Soft Tissue Research, Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York, NY 10021-4010, USA. torzillip@hss.edu
Bhargava
M
M
Park
S
S
Chen
C T C
CT
D053674:Aggrecans / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002417:Cattle; D003094:Collagen / Q000378:metabolism*; D010450:Endopeptidases / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000276:immunology / Q000378:metabolism; D013314:Stress, Mechanical
D053674:Aggrecans; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D003094:Collagen; D010450:Endopeptidases; D020782:Matrix Metalloproteinases; C083641:aggrecanase