MOLECULAR MECHANISMS OF CYTOKINE-INDUCED CARTILAGE DESTRUCTION IN RHEUMATOID ARTHRITIS

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes long-term destruction of cartilage and leads to irreversible arthritis. Pro-inflammatory messengers such as interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF alpha), interleukin-6 (IL-6), and interleukin-17 (IL-17)—drive this destructive process by targeting cells in joint tissue. Once released, these signals activate known pathways within chondrocytes and synovial fibroblasts, like NF-kappa B, MAPKs, and JAK-STAT, prompting these cells to produce destructive enzymes such as matrix metalloproteinases (MMPs) and aggrecans (ADAMTS). Because the production of these enzymes exceeds tissue repair, the cartilage structure—a mesh of type II collagen and aggrecan—begins to break down, leading to pain and disability. Additionally, cytokine-mediated chondrocyte apoptosis and phenotypic changes contribute to impaired cartilage repair and ongoing inflammation. Epigenetic modifications, including DNA methylation (DNAme) and microRNA (miRNA)-mediated regulation, influence cytokine functions in chondrocytes and may serve as therapeutic targets. Current RA treatments include TNF inhibitors, IL-6 receptor blockers, and JAK inhibitors that aim to block cytokine signalling pathways to slow disease progression. In addition, the development of targeted therapies, such as selective inhibitors of ADAMTS-5 and epigenetic regulators, offers hope for improved cartilage protection in RA. Understanding this complex network of cytokines, signalling pathways, and effector enzymes involved in cartilage destruction is essential for developing new disease-modifying strategies for RA.