Osteoimmunology in rheumatic diseases

Abstract

This review summarizes the recent advances of osteoimmunology, a new research field that investigates the interaction of the immune system with the skeleton. Osteoimmunology has contributed significantly to the understanding of joint destruction in rheumatoid arthritis and other forms of arthropathies. In particular, the molecular regulation of osteoclast formation and its control by proinflammatory cytokines have helped investigators to understand the mechanisms of bone erosion in rheumatic diseases. Osteoimmunology has also allowed an improvement in our knowledge of the structure-sparing effects of antirheumatic drug therapy. Moreover, recent advances in the understanding of the molecular regulation of osteophyte formation are based on the characterization of the regulation of bone formation by inflammation. This review highlights the key insights into the regulation of bone destruction and formation in arthritis. Moreover, concepts of how bone influences the immune system are discussed.

Figure 1

Osteoclast formation in the joint. Monocytic cells in the synovium serve as osteoclast precursors. Upon exposure to macrophage colony-stimulating factor (MCSF) and RANKL synthesized by T cells and synovial fibroblasts, osteoclasts fuse to polykaryons termed preosteoclasts, which then undergo further differentiation into mature osteoclasts, acquiring specific features such as the ruffled membrane. Inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1, IL-6, and IL-17 increase the expression of RANKL and thus support osteoclastogenesis in the joint. In contrast, regulatory T (Treg) cells block osteoclast formation via CTLA4. RANKL, receptor activator of nuclear factor-kappa B ligand.

Figure 2

Bone marrow niche. Pre-pro-B cells share a common niche with plasma cells based on the expression of CXC chemokine ligand-12 (CXCL12) by bone marrow stromal cells. Upon further differentiation into pro-B cells, cells switch to a different niche, which is based on interleukin-7 (IL-7)-expressing bone marrow stromal cells. Further differentiation of B cells into pre-B cells makes them independent from bone marrow niches before leaving bone marrow to secondary lymphatic organs. Plasma cells re-entering the bone marrow share the CXCL12-triggered bone marrow niche with pre-pro B cells, as described above. Hematopoietic stem cells (HSCs) are linked to bone marrow niches created by osteoblasts.