Proteoglycan degradation after injurious compression of bovine and human articular cartilage in vitro: interaction with exogenous cytokines

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Patwari, Parth¹; Cook, Michael N.²; DiMicco, Michael A.¹; Blake, Simon M.²; James, Ian E.²; Kumar, Sanjay²; Cole, Ada A.³; Lark, Michael W.²; Grodzinsky, Alan J.¹

Proteoglycan degradation after injurious compression of bovine and human articular cartilage in vitro: interaction with exogenous cytokines

Arthritis Rheum. May 2003;48(5):1292-1301

©2003 American College of Rheumatology

Affiliations

¹Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts

²Glaxo SmithKline, King of Prussia, Pennsylvania

³Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, Illinois
Abstract

Objective: Traumatic joint injury leads to an increased risk of osteoarthritis (OA), but the progression to OA is not well understood. We undertook this study to measure aspects of proteoglycan (PG) degradation after in vitro injurious mechanical compression, including up-regulation of enzymatic degradative expression and cytokine-stimulated degradation.

Methods: Articular cartilage tissue explants were obtained from newborn bovine femoropatellar groove and from adult normal human donor knee and ankle tissue. Following injurious compression of the cartilage, matrix metalloproteinase 3 (MMP-3) and MMP-13 messenger RNA (mRNA) expression levels were measured by Northern analysis, and PG loss to the medium after cartilage injury was measured in the presence and absence of added exogenous cytokine (interleukin-1α [IL-1α] or tumor necrosis factor α [TNFα]).

Results: During the first 24 hours after injury in bovine cartilage, MMP-3 mRNA levels increased 10-fold over the levels in control cartilage (n = 3 experiments), whereas MMP-13 mRNA levels were unchanged. PG loss was significantly increased after injury, but only by 2% of the total PG content and only for the first 3 days following injury. However, compared with injury alone or cytokine treatment alone, treatment of injured tissue with either 1 ng/ml IL-1α or 100 ng/ml TNFα caused marked increases in PG loss (35% and 54%, respectively, of the total cartilage PG content). These interactions between cytokine treatment and injury were statistically significant. In human knee cartilage, the interaction was also significant for both IL-1α and TNFα, although the magnitude of increase in PG loss was lower than that in bovine cartilage. In contrast, in human ankle cartilage, there was no significant interaction between injury and IL-1α.

Conclusion: The cytokines IL-1α and TNFα can cause a synergistic loss of PG from mechanically injured bovine and human cartilage. By attempting to incorporate interactions with other joint tissues that may be sources of cytokines, in vitro models of mechanical cartilage injury may explain aspects of the interactions between mechanical forces and degradative pathways which lead to OA progression.
Links

DOI: 10.1002/art.10892

PubMed: 12746902

WoS: 000182736600014
History

Received: 2002-10-08

Accepted: 2003-01-03

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