The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive

Abstract

Although osteoarthritis (OA) has existed since the dawn of humanity, its pathogenesis remains poorly understood. OA is no longer considered a "wear and tear" condition but rather one driven by proteases where chronic low-grade inflammation may play a role in perpetuating proteolytic activity. While multiple factors are likely active in this process, recent evidence has implicated the innate immune system, the older or more primitive part of the body's immune defense mechanisms. The roles of some of the components of the innate immune system have been tested in OA models in vivo including the roles of synovial macrophages and the complement system. This review is a selective overview of a large and evolving field. Insights into these mechanisms might inform our ability to identify patient subsets and give hope for the advent of novel OA therapies.

Keywords: COMPLEMENT; INNATE IMMUNITY; MACROPHAGES; OSTEOARTHRITIS.

Figure 1. Osteoarthritis Pathogenesis

This figure depicts the self-perpetuating cycle of joint degeneration that characterizes the pathogenesis of osteoarthritis. In this paradigm, an inciting injury to the joint tissue causes the breakdown of the extracellular matrix (ECM), which initiates activation of innate immunity and a cyclic cascade of inflammatory events leading to further and ongoing joint damage.

Figure 2. The Complement System

The complement cascade is a complex system that can become activated by one of three separate pathways: the classical, the mannose-binding (MB)-Lectin and alternative pathways. All three pathways converge on the C3 protein. C3 cleavage products participate in the activation of C5 whose cleaved components contribute to a local inflammatory response (C5a) or form part of the membrane attack complex that plays a role in cell lysis (C5b). Abbreviations: CD, cluster of differentiation; H, complement factor H; MAC, membrane attack complex; MASP, mannan-binding lectin serine protease; MB, mannose binding; MBL, mannose binding lectin. Complement effectors=blue, complement inhibitors=red. Adapted from Wang 2011 (35) and Sturfelt 2012 (51).