, Volume 18, Issue 1, pp 23–35

Cytokines as Therapeutic Targets for Osteoarthritis

Novel Therapeutic Strategies

DOI: 10.2165/00063030-200418010-00003

Cite this article as:
Malemud, C.J. BioDrugs (2004) 18: 23. doi:10.2165/00063030-200418010-00003


Osteoarthritis (OA) is a debilitating, progressive disease of diarthrodial joints associated with the aging process. With the exception of anti-inflammatory corticosteroids and nonsteroidal anti-inflammatory drugs which inhibit cyclo-oxygenase-2, the enzyme responsible for prostaglandin biosynthesis in inflammation, no specific therapy based on fundamental intracellular pathways of chondrocytes and synoviocytes exists for the medical management of OA. At the molecular level, OA is characterized by an imbalance between chondrocyte anabolism and catabolism. Disruption of chondrocyte homeostasis primarily affects the cartilage extracellular matrix (ECM), which is responsible for the biomechanical properties of the tissue. Recent evidence has implicated cytokines, among which interleukin (IL)-1, tumor necrosis factor-α, IL-6, and IL-17 seem most involved in the OA process of cartilage destruction. The primary role of these cytokines is to modulate the expression of matrix metalloproteinases and cartilage ECM proteins. Cartilage repair that could restore the functional integrity of the joint is also impaired because chondrocytes in OA cartilage appear unable to respond to insulin-like growth factor-1 or respond abnormally to transforming growth factor-β. As these growth factors also modulate cytokine expression, they may prove useful in designing strategies for suppressing ‘chondrocyte activation’. Although cytokines and growth factors provide a potential therapeutic target for OA, it will be necessary to elucidate the fundamental mechanisms that cytokines employ to cause chondrocyte and synoviocyte dysfunction before ‘anti-cytokine’ therapy can be employed in the medical management of the disease.

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Departments of Medicine and AnatomyCase Western Reserve University School of MedicineClevelandUSA
  2. 2.Department of Medicine, Division of Rheumatic DiseasesUniversity Hospitals of ClevelandClevelandUSA