Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n‐3 fatty acids

Abstract

Objective: To determine if n‐3 polyunsaturated fatty acid (PUFA) supplementation (versus treatment with n‐6 polyunsaturated or other fatty acid supplements) affects the metabolism of osteoarthritic (OA) cartilage. Methods: The metabolic profile of human OA cartilage was determined at the time of harvest and after 24‐hour exposure to n‐3 PUFAs or other classes of fatty acids, followed by explant culture for 4 days in the presence or absence of interleukin‐1 (IL‐1). Parameters measured were glycosaminoglycan release, aggrecanase and matrix metalloproteinase (MMP) activity, and the levels of expression of messenger RNA (mRNA) for mediators of inflammation, aggrecanases, MMPs, and their natural tissue inhibitors (tissue inhibitors of metalloproteinases [TIMPs]). Results: Supplementation with n‐3 PUFA (but not other fatty acids) reduced, in a dose‐dependent manner, the endogenous and IL‐1–induced release of proteoglycan metabolites from articular cartilage explants and specifically abolished endogenous aggrecanase and collagenase proteolytic activity. Similarly, expression of mRNA for ADAMTS‐4, MMP‐13, and MMP‐3 (but not TIMP‐1, ‐2, or ‐3) was also specifically abolished with n‐3 PUFA supplementation. In addition, n‐3 PUFA supplementation abolished the expression of mRNA for mediators of inflammation (cyclooxygenase 2, 5‐lipoxygenase, 5‐lipoxygenase–activating protein, tumor necrosis factor α, IL‐1α, and IL‐1β) without affecting the expression of message for several other proteins involved in normal tissue homeostasis. Conclusion: These studies show that the pathologic indicators manifested in human OA cartilage can be significantly altered by exposure of the cartilage to n‐3 PUFA, but not to other classes of fatty acids.