The Role of Inflammation in the Pathogenesis of Osteoarthritis

Abstract

A joint is the point of connection between two bones in our body. Inflammation of the joint leads to several diseases, including osteoarthritis, which is the concern of this review. Osteoarthritis is a common chronic debilitating joint disease mainly affecting the elderly. Several studies showed that inflammation triggered by factors like biomechanical stress is involved in the development of osteoarthritis. This stimulates the release of early-stage inflammatory cytokines like interleukin-1 beta (IL-1β), which in turn induces the activation of signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and mitogen-activated protein kinase (MAPK). These events, in turn, generate more inflammatory molecules. Subsequently, collagenase like matrix metalloproteinases-13 (MMP-13) will degrade the extracellular matrix. As a result, anatomical and physiological functions of the joint are altered. This review is aimed at summarizing the previous studies highlighting the involvement of inflammation in the pathogenesis of osteoarthritis.

Figure 1

The signaling pathways (brown, grey, and purple box) involved and interactions between cytokines (pink box), chemokines (beige box), matrix metalloproteinases (green box), and other proteins in osteoarthritis. IL-1β and TNF-α (pink box) produced by cells; for example, activated chondrocytes, synoviocytes, and mononuclear cells are among the early mediators in the inflammatory cascades. Continuous lines indicate stimulation while dotted lines indicate inhibition of the downstream molecule or activity. The outcomes of the molecule interactions are shown in yellow boxes.

Figure 2

Alteration of miRNA levels in osteoarthritis and its downstream influences.