Innate immune system activation in osteoarthritis: is... : Current Opinion in Rheumatology (original) (raw)

Osteoarthritis: Edited by Kenneth C. Kalunian

aHospital for Special Surgery, Division of Rheumatology, New York, New York, USA

bRush University Medical Center, Department of Internal Medicine (Rheumatology) and Biochemistry, Chicago, Illinois, USA

Correspondence to Carla R. Scanzello, Rush University Medical Center, Section of Rheumatology, 1725W Harrison Street, Suite 1017, Chicago, IL 60612, USA Tel: +1 312 942 8268; fax: +1 312 563 2267; e-mail: [email protected]

Abstract

Purpose of review

Synovial inflammation is increasingly recognized as an important pathophysiologic process in osteoarthritis, but the stimuli and downstream pathways activated are not well defined. Innate immune system activation, best documented in responses to pathogens, likely plays a role in induction of inflammatory mediators and the specific cellular infiltrate seen in osteoarthritis. Thus, the Toll-like receptors (TLRs) and their signaling pathways are of particular interest. These innate pattern-recognition receptors are activated not only by pathogens but by endogenous ‘danger signals’. In this report, we review evidence that certain extracellular matrix components of joint tissues (hyaluronan and fibronectin) may act as TLR stimuli, and summarize recent literature implicating TLR activation in osteoarthritis.

Recent findings

Convincing evidence exists that hyaluronan/TLR interactions drive responses to tissue injury. Evidence of a similar role for fibronectin is growing. TLRs are expressed and functional in the joint, and many proteases and cytokines that promote cartilage catabolism are dependent on nuclear factor-κB, a TLR-activated transcription factor.

Summary

Activation of TLR pathways seems likely in osteoarthritis and may play a central role in disease development and progression. A model of osteoarthritis as a chronic wound, in which the innate immune response is triggered by molecular signals of tissue damage, is presented as a framework for future study of inflammation in this prevalent joint disease.