T-cell involvement in osteoclast biology: implications for rheumatoid bone erosion.

Erosion of periarticular bone is a hallmark of rheumatoid arthritis (RA), resulting in significant joint deformity, pain and disability [1]. Osteoclasts are specialized cells of the macrophage lineage responsible for bone resorption during remodelling. These cells have been demonstrated at the site of erosion in RA [2, 3] and in representative animal models of the disease [4], and are thus believed to be critical in the pathogenesis of joint damage. Developments in research methods have facilitated significant advances in the understanding of osteoclast regulation in conditions characterized by excessive bone resorption, including RA. As the osteoblast-derived signal that regulates osteoclasts [receptor activator of nuclear factor B ligand (RANKL); see below] is identical to TRANCE (tumour necrosis factor-related activation-induced cytokine), which was first discovered in studies of T cells [5, 6], the intriguing role of T cells in bone biology has generated a considerable literature, referred to as ‘osteoimmunology’ [7]. In this article we will briefly describe normal bone remodelling and RANKL expression by T cells in the interaction with dendritic cells (DCs). Osteoclast regulation by T-cell expression of RANKL and other cytokines will then be described in the setting of the three clinical conditions most commonly studied—RA and its animal models, osteoporosis, and adult periodontitis. Potential therapeutic strategies for the prevention of bone loss in RA will be highlighted.