The role of proinflammatory cytokines in osteoarthritis: New therapeutic approaches using anti-cytokine therapy and NF-κB inhibitors

Mobasheri, A and Shakibaei, M (2012) The role of proinflammatory cytokines in osteoarthritis: New therapeutic approaches using anti-cytokine therapy and NF-κB inhibitors pp. 147-169.

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Abstract

Osteoarthritis (OA) is the most common form of joint disease. It is the most common cause of chronic disability in older adults. OA has enormous socioeconomic consequences for healthcare systems in North America, Europe and throughout the rest of the developed world. OA is associated with articular cartilage destruction, subchondral bone remodeling and synovial thickening. Although OA was traditionally viewed as a "wear and tear" degenerative condition of synovial joints, recent studies have demonstrated a significant inflammatory component to the disease, which includes increased expression and activity of several secreted proinflammatory cytokines in the joint tissues that drive production of matrix-degrading enzymes. Interleukin 1ß (IL-1ß) and tumor necrosis factor a (TNF-a) are key cytokines involved in degeneration of articular cartilage matrix, which makes them and their downstream signaling pathways prime targets for novel therapeutic strategies. Apart from IL-1ß and TNF-a, several other cytokines and chemokines including IL-6, IL-8 and IL-17 are implicated in OA. These proinflammatory cytokines bind to their respective cell surface receptors and activate inflammatory signaling pathways culminating with the activation of nuclear factor κB (NF-κB) a transcription factor that can be triggered by stress-related stimuli, including excessive mechanical stress and extracellular matrix (ECM) degradation products. Once activated, NF-κB regulates the expression of many cytokines, chemokines, adhesion molecules, inflammatory mediators, and several matrix-degrading enzymes. Therefore, proinflammatory cytokines and their cell surface receptors, as well as NF-κB and associated signaling pathways can be targeted in OA. This chapter reviews the current state of play regarding the role of proinflammatory cytokines in the pathophysiology of OA, and addresses the potential of anti-cytokine and anti-NF-κB therapy in the treatment of this disease. We also discuss the potential for complementary therapies using natural products such as curcumin and resveratrol. © 2012 by Nova Science Publishers, Inc. All rights reserved.

Item Type:	Article
Authors :	Name Email ORCID Mobasheri, A a.mobasheri@surrey.ac.uk Shakibaei, M
Date :	1 January 2012
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 10:12
Last Modified :	17 May 2017 14:48
URI:	http://epubs.surrey.ac.uk/id/eprint/826840

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