Bone is continuously renewed through a dynamic balance between bone resorption and formation. This process is the fundamental basis for the maintenance of normal bone mass and architecture. Osteoclasts play a crucial role in both physiological and pathological bone resorption, and receptor activator of nuclear factor-κB ligand (RANKL) is the key cytokine that induces osteoclastogenesis. Here we summarize the recent advances in the understanding of osteoclastogenic signaling by focusing on the investigation of RANKL signaling and RANKL-expressing cells in the context of osteoimmunology. The context afforded by osteoimmunology will provide a scientific basis for future therapeutic approaches to diseases related to the skeletal and immune systems.
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