Orthodontic tooth movement (OTM) is achieved by the simultaneous activation of bone resorption by osteoclasts and bone formation by osteoblasts. When orthodontic forces are applied, osteoclast-mediated bone resorption occurs in the alveolar bone on the compression side, creating space for tooth movement. Therefore, controlling osteoclastogenesis is the fundamental tenet of orthodontic treatment. Orthodontic forces are sensed by osteoblast lineage cells such as periodontal ligament (PDL) cells and osteocytes. Of several cytokines produced by these cells, the most important cytokine promoting osteoclastogenesis is the receptor activator of nuclear factor-κB ligand (RANKL), which is mainly supplied by osteoblasts. Additionally, osteocytes embedded within the bone matrix, T lymphocytes in inflammatory conditions, and PDL cells produce RANKL. Besides RANKL, inflammatory cytokines, such as interleukin-1, tumor necrosis factor-α, and prostaglandin E2 promote osteoclastogenesis under OTM. On the downside, excessive osteoclastogenesis activation triggers orthodontically-induced external root resorption (ERR) through pro-osteoclastic inflammatory cytokines. Therefore, understanding the mechanisms of osteoclastogenesis during OTM is essential in reducing the adverse effects of orthodontic treatment. Here, we review the current concepts of the mechanisms underlying osteoclastogenesis in OTM and orthodontically induced ERR.
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