Pathomechanisms of bone loss in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease, in which the inflammatory processes involve the skeletal system and there is marked destruction of the bones and the surrounding structures. In this review, we discuss the current concepts of osteoimmunology in RA, which represent the molecular crosstalk between the immune and skeletal systems, resulting in the disruption of bone remodeling. Bone loss in RA can be focal or generalized, leading to secondary osteoporosis. We have summarized the recent studies of bone loss in RA, which focused on the molecular aspects, such as cytokines, autoantibodies, receptor activator of nuclear kappa-β ligand (RANKL) and osteoprotegerin (OPG). Apart from the above molecules, the role of aryl hydrocarbon receptor (Ahr), which is a potential key mediator in this process through the generation of the Th17 cells, is discussed. Hence, this review highlights the key insights into molecular mechanisms of bone loss in RA.

Keywords: autoantibodies; bone; cytokines; ligands; osteoporosis; rheumatoid arthritis.

Figure 1

RANKL-dependent osteoclastogenesis.

Figure 2

The effects of tumor necrosis factor inhibitors on RA-related bone loss. TRAF6, TNF-receptor associated factor-6; FRA-2, Fos-related antigen-2; AP-1, Activator protein 1; RANK, receptor activator of nuclear factor kappa-B; RANKL, Receptor activator of nuclear factor kappa-B ligand.

Figure 3

The role of the key cytokines in osteoclastogenesis. IL, Interleukin; NF, Tumor Necrosis factor; RANKL, Receptor activator of nuclear factor kappa-B ligand; PICP, propeptides of type I procollagen; PINP, N-terminal propeptides of type I procollagen; CTX 1, carboxy-terminal crosslinked telopeptide of type 1 collagen; NTX 1, amino-terminal crosslinked telopeptide of type 1 collagen; PGE, prostaglandin; MAPK, mitogen-activated protein kinase; DKK1, Dickkopf WNT signaling pathway inhibitor 1; SOST, Sclerostin.

Figure 4

Anti-CCP and osteoclastogenesis.

Figure 5

The mechanism of osteogenesis inhibition by Ahr-associated mesenchymal stem cell via the Wnt/-catenin pathway. Ahr, aryl hydrocarbon receptor; ERK1/2, extracellular signal_regulated protein kinase; MAPK, mitogen-activated protein kinase.