Role of Circulating Monocytes and Periodontopathic Bacteria in Pathophysiology of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is characterized by chronic inflammation in the synovial membrane, leading to matrix destruction of cartilage and bone. While various types of immune cell are found in inflamed synovium in RA, macrophages and osteoclasts also play important roles in joint destruction. Peripheral blood monocytes migrate to synovial tissue and differentiate into macrophages and osteoclasts in RA. Synovial macrophages are classified into two subsets: M1 (proinflammatory macrophages) or M2 (anti-proinflammatory macrophages). Human circulating monocytes have also been divided into three subsets according expression level of CD14 and CD16: CD14⁺CD16^- (classical); CD14^brightCD16⁺ (intermediate); or CD14^dimCD16⁺ (non-classical). Many recent studies have investigated the involvement of each subset of synovial macrophages and circulating monocytes in the pathophysiology of RA. On the other hand, several distinct human cell populations originating in circulating monocytes have the capacity to differentiate into non-phagocytic cells, including endothelial cells and adipocytes. This review summarizes the role of circulating monocytes in the pathophysiology of RA as precursor cells of not only phagocytes, such as macrophages and osteoclasts, but also non-phagocytes, such as endothelial cells and adipocytes. Furthermore, there is a growing body of evidence showing a significantly positive association between periodontopathic bacterial infection and the pathophysiology of RA. Therefore, the role of periodontopathic bacteria in the development of RA is also discussed.