IBMS BoneKEy | Perspective
Control of osteoclast precursor migration: A novel point of control for osteoclastogenesis and bone homeostasis
Taeko Ishii
Junichi Kikuta
Atsuko Kubo
Masaru Ishii
DOI:10.1138/20100459
Abstract
Osteoclasts are bone-resorbing, multinucleated giant cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursors. They have critical roles not only in normal bone remodeling but also during pathogenesis of destructive bone disorders such as osteoporosis, rheumatoid arthritis, and cancers metastatic to bone. Many molecules, especially macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL), make significant contributions to osteoclast differentiation. However, the process of osteoclast precursor trafficking to and from the bone surface, where cell fusion occurs to form the fully differentiated multinucleated cells that mediate bone resorption, is less well-documented. Recent studies have shed light on the mechanisms involved and have demonstrated the vital participation of various chemokines such as CCL2, CCL5, CXCL12, and CX3CL1, and lipid mediators such as sphingosine-1-phosphate (S1P). In addition, advances in imaging technologies, such as the development of intravital multiphoton microscopy, have enabled the in situ visualization of the behavior of osteoclasts and their precursors within intact bone tissue. This capability will be extremely useful for dissecting the mechanisms controlling the migration of these cells in vivo. In this Perspective, we review the latest knowledge in this new field of bone biology, with a focus on novel imaging methodology and its applications in this field.
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