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Osteoclasts are tissue-specific, large, multinucleated macrophages derived from monocyte/macrophage precursors at or near the bone surface.
The close contact between stromal and bone marrow cells generate RANKL and CSF-1 that can induce expression of genes that typify osteoclast lineage, including TRAP, CATK, calcitonin receptor, and β3-integrin, leading to the development of mature osteoclasts (osteoclastogenesis). Certain hormones, cytokines, and humoral factors produced in distant organs can also influence bone density and calcium homeostasis locally by inducing RANKL expression within the bone cells. The RANK signaling pathway is tightly controlled, and there is also evidence of feedback mechanism that can switch off the RANK signaling once it is activated.
A mature, activated osteoclast functions as bone-degrading cell by forming a tight junction between the bone surface and basal membrane, acidifying the sealed external vacuole, and secreting lytic enzymes into a resorption pit (Howship’s lacuna). Degradation products, including collagen fragments and solubilized calcium and phosphate, are processed within the osteoclast and released into the circulation.
Together, the cross-talk between osteoblasts and osteoclasts coordinates the bone remodeling process. Osteoblasts facilitate bone synthesis, whereas osteoclasts are responsible for bone resorption; however, it has been shown that RANKL expression by osteoblasts stimulate local osteoclasts, which in turn can further stimulate osteoblasts by a process called “coupling”. Humoral factors that decrease bone resorption and increase bone density, such as estrogens, have a converse effect on the coupling between the osteoblast and osteoclast.
CATK: cathepsin K; CSF: colony-stimulating factor; TRAP: tartrate-resistant acid phosphatase; RANK: receptor activator of nuclear factor-kappaB; RANKL: RANK ligand.
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