The pro-inflammatory niche: how the extracellular matrix drives rheumatoid arthritis?

Abstract

Introduction: The extracellular matrix is a complex, three-dimensional network of secreted molecules that provides structural support to tissues and environmental cues to the cells within. One particular subset of matrix molecules is specifically ex- pressed upon tissue damage. These molecules contribute to effective tissue repair by orchestrating the behaviour of cells that mediate this process, and once the repair is complete, the expression of this matrix is downregulated. Here, we focus on the recent data that highlights a direct role for injury-induced matrix molecules in driving inflammation upon tissue damage and propose that this matrix creates a specific microenvironment or ‘pro-inflammatory niche’ that is permissive for localized inflammation during repair. We also examine the evidence indicating that this niche exists, and persists, in the damaged joint of rheumatoid arthritis patients. Finally, we assess the data which demonstrate that these matrix molecules actively contribute to maintaining chronic inflammation during disease progression. Conclusion: Together these findings imply that targeting the pro-inflammatory niche in the joint may provide a novel treatment strategy for rheumatoid arthritis.