Osteoclasts, Rheumatoid Arthritis, and Osteoimmunology
Osteoclasts, Rheumatoid Arthritis, and Osteoimmunology
Purpose of Review: Osteoclasts are terminally differentiated cells of the monocyte/macrophage lineage that resorb bone matrix. Bone destruction in rheumatoid arthritis is mainly attributable to the abnormal activation of osteoclasts, and studies on activation of osteoclasts by the immune system have led to the new research field called osteoimmunology. This interdisciplinary field is very important to biologic research and to the treatment of diseases associated with the bone and immune systems.
Recent Findings: The T-cell-mediated regulation of osteoclast differentiation is dependent on cytokines and membrane-bound factors expressed by T cells. The cross-talk between receptor activator of nuclear factor-κB ligand and inteferon-γ has been shown to be crucial for the regulation of osteoclast formation in arthritic joints. Recent studies indicate that an increasing number of immunomodulatory factors are associated with the regulation of bone metabolism: nuclear factor of activated T cells c1 has been shown to be the key transcription factor for osteoclastogenesis, the activation of which requires calcium signaling induced by the immunoglobulin-like receptors.
Summary: New findings in osteoimmunology will be instrumental in the development of strategies for research into the treatment of various diseases afflicting the skeletal and immune systems.
Bone is important not only in the skeletal system: it serves as a reservoir of inorganic ions such as calcium and provides a site for hematopoiesis. This multifunctional organ is closely related to the immune system, the cells of which are generated in and inhabit the bone marrow. Although bone appears to be inert, it is a dynamic tissue that is constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. Dysfunction or imbalance of these cells is very often related to the various metabolic bone diseases. For example, hyperactivation of osteoclasts is observed in rheumatoid arthritis (RA) and postmenopausal osteoporosis. Thus, it is not only biologically but also clinically of great importance to identify the mechanisms underlying osteoclast differentiation and function.
Abstract and Introduction
Abstract
Purpose of Review: Osteoclasts are terminally differentiated cells of the monocyte/macrophage lineage that resorb bone matrix. Bone destruction in rheumatoid arthritis is mainly attributable to the abnormal activation of osteoclasts, and studies on activation of osteoclasts by the immune system have led to the new research field called osteoimmunology. This interdisciplinary field is very important to biologic research and to the treatment of diseases associated with the bone and immune systems.
Recent Findings: The T-cell-mediated regulation of osteoclast differentiation is dependent on cytokines and membrane-bound factors expressed by T cells. The cross-talk between receptor activator of nuclear factor-κB ligand and inteferon-γ has been shown to be crucial for the regulation of osteoclast formation in arthritic joints. Recent studies indicate that an increasing number of immunomodulatory factors are associated with the regulation of bone metabolism: nuclear factor of activated T cells c1 has been shown to be the key transcription factor for osteoclastogenesis, the activation of which requires calcium signaling induced by the immunoglobulin-like receptors.
Summary: New findings in osteoimmunology will be instrumental in the development of strategies for research into the treatment of various diseases afflicting the skeletal and immune systems.
Introduction
Bone is important not only in the skeletal system: it serves as a reservoir of inorganic ions such as calcium and provides a site for hematopoiesis. This multifunctional organ is closely related to the immune system, the cells of which are generated in and inhabit the bone marrow. Although bone appears to be inert, it is a dynamic tissue that is constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. Dysfunction or imbalance of these cells is very often related to the various metabolic bone diseases. For example, hyperactivation of osteoclasts is observed in rheumatoid arthritis (RA) and postmenopausal osteoporosis. Thus, it is not only biologically but also clinically of great importance to identify the mechanisms underlying osteoclast differentiation and function.
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