Mechanisms of Synovitis—Impact on the Skeletal Environment

Abstract

Abstract
In rheumatoid arthritis (RA), inflammation within the synovium, or synovitis, results in articular bone erosion, which contributes to long-term disability from this disease. Osteoclasts are essential cells that mediate bone erosions in the inflammatory skeletal milieu. The receptor activator of nuclear factor kappa-B (NFκB) ligand (RANKL)/RANK signaling pathway promotes osteoclastogenesis, while osteoprotegerin (OPG), a decoy receptor for RANKL, inhibits osteoclastogenesis. These factors are important regulators in osteoclast-driven bone resorption in the inflamed joint in RA. Other proinflammatory cytokines, most notably tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and IL-17, expressed in the inflamed synovium, can also promote osteoclast differentiation, function, and/or survival. Modulation of these and other factors that promote osteoclastogenesis holds promise in the prevention and treatment of inflammation-induced articular bone loss in RA.

Keywords
Synovitis, erosions, osteoclasts, tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-6, IL-17

Disclosure: Sangeetha Balasubramanian, MD, has no conflicts of interest to declare. Ellen M Gravallese, MD, is a consultant for the Abbott Bioresearch Center, and receives grant funding from Biogen Idec, Inc.
Received: December 7, 2009 Accepted: February 26, 2010 Citation: US Musculoskeletal Review, 2010;5:75–80
Correspondence: Ellen M Gravallese, MD, University of Massachusetts Medical School, Lazare Research Building, Suite 223, 364 Plantation Street, Worcester, MA 01605. E: ellen.gravallese@umassmed.edu