[CITATION][C] The role of osteoprotegerin and receptor activator of nuclear factor κB ligand in the pathogenesis and treatment of rheumatoid arthritis

LC Hofbauer, AE Heufelder - Arthritis & Rheumatism: Official …, 2001 - Wiley Online Library
LC Hofbauer, AE Heufelder
Arthritis & Rheumatism: Official Journal of the American College …, 2001Wiley Online Library
The skeletal complications of rheumatoid arthritis (RA) include focal bone erosions and
juxtaarticular osteopenia at sites of active inflammation, as well as systemic osteopenia,
resulting in significant joint deformity, disability, and pain in addition to an increased risk of
bone fractures (1, 2). Several lines of evidence have clearly established that osteoclasts,
multinucleated cells of the monocyte/macrophage lineage, are key mediators of bone loss in
RA (2–4). Activated T cells, a proinflammatory cytokine milieu, and their interactions with …
The skeletal complications of rheumatoid arthritis (RA) include focal bone erosions and juxtaarticular osteopenia at sites of active inflammation, as well as systemic osteopenia, resulting in significant joint deformity, disability, and pain in addition to an increased risk of bone fractures (1, 2). Several lines of evidence have clearly established that osteoclasts, multinucleated cells of the monocyte/macrophage lineage, are key mediators of bone loss in RA (2–4). Activated T cells, a proinflammatory cytokine milieu, and their interactions with cells of the bone microenvironment and the immune system have been suggested as potential mechanisms that promote the differentiation and activation of osteoclasts and lead to enhanced bone resorption (2). The recent identification and characterization of receptor activator of nuclear factor B ligand (RANKL), an essential cytokine for various osteoclast functions, its receptor, receptor activator of nuclear factor B (RANK), and its decoy receptor, osteoprotegerin (OPG), have created a new molecular and cellular concept of osteoclast biology, bone resorption, and bone and cartilage homeostasis (5–7)(Table 1). The fact that RANK is expressed on osteoclasts and dendritic cells (DCs), that RANKL regulates important functions of osteoclasts, DCs, and T cells, and that bone marrow stromal cells and activated T cells produce RANKL suggests common paracrine pathways in the regulation of bone metabolism and immune functions. In this article, we highlight the potential roles of RANKL, RANK, and OPG in the pathogenesis and treatment of skeletal lesions in RA.
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