Role of Bone Marrow in the Pathogenesis of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent synovial proliferation. Thus, joints in RA consist of massive proliferating synovium, forming an invading tissue termed pannus, which results in the destruction of cartilage and bone. One of the most important histologic characteristics of the synovium in RA includes cellular proliferation in the lining layer as well as in the sublining layer (Tak, 2004). In the lining layer, both type A and type B synoviocytes, alternatively called intimal macrophages and fibroblast-like synoviocytes, respectively, are found to proliferate (Tak, 2004). In the sublining layer, there is infiltration of a variety of cells, including dendritis cells (DC), lymphocytes, plasma cells, and polymorphnuclear leukocytes. Notably, lymphoid cluster in RA synovium sometimes forms pseudo-germinal center, consisting of CD20+ B cells in the center surrounded by CD4+ T cells (Tak, 2004; Hirohata, 2004). In the synovium of RA, neovascularization is usually accompanied by lining cell proliferation and inflammatory cell infiltration (Firestein, 1999). In fact, lining cells and inflammatory cells have been found to produce angiogenic growth factors (Koch, 1998). It should be noted, however, that the synovium of RA also showed neovascularization in the areas without either lining cell proliferation or inflammatory cell infiltration, suggesting that the neovascularization might be one of the primary abnormal features that are most proximal to the etiology of RA (Hirohata & Sakakibara, 1999). A number of studies have suggested that abnormal activation of normal joint constituents, such as synovial lining cells, play a pivotal role in the synovial hyperplasia in RA (Shiozawa & Tokuhisa, 1992). However, increasing attention has emerged to the role of bone marrow in the pathogenesis of RA. The present article overviews an update on the role of bone marrow in the pathogenesis of RA.