Figure 1

Cells involved in rheumatoid arthritis joint damage include osteoblasts, osteoclasts, chondrocytes, monocytes/macrophages, B cells, T cell subsets (including regulatory T cells), and fibrobast-like synoviocytes, each playing distinct complex and interrelated roles in its pathogenesis and progression. This cellular diversity highlights the need for biomarkers for a range of pathological events. Different markers of cell signaling (for example, receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG)), cell differentiation, collagen I and II degradation and turnover, matrix production, and matrix degradation and the enzymes mediating that degradation may be measured. The pleiotrophic cytokines IL-1β, TNF-α, IL-6, and IL-17, as well as several other cytokines and chemokines, are associated with the induction of matrix metalloproteinases (MMPs), as well as osteoclast differentiation, activation and release of cathepsin K [36]. This range of interactive events leads to progressive joint destruction if not managed attentively, for example, using tight control strategies [15, 18, 22, 104, 140, 141]. C2C, type II collagen fragment; CIIM, MMP mediated type II collagen degradation; CTX-I, C-terminal telopeptide of collagen type I; CTX-II, C-terminal telopeptide of collagen type II.