Pathogenesis of Metastatic Calcification and Acute Pancreatitis in Adult T-Cell Leukemia under Hypercalcemic State

Figure 4

Molecular mechanism of osteoclast differentiation and activation involving the RANKL/RANK/OPG system. Bone remodeling is a balance between formation and resorption through the control of osteoblast and osteoclast activities. Receptor activator of nuclear factor-κB ligand (RANKL), receptor activator of nuclear factor-κB (RANK), and osteoprotegerin (OPG) play important roles in bone remodeling and disorders of mineral metabolism. Bone resorbing factors, such as PTH, PTHrP, IL-1, IL-6, IL-11, and 1α,25(OH)₂D₃, act on osteoblasts to induce the membrane associated factor called RANKL, which recognizes RANK present on the surface of osteoclast progenitors and osteoclasts. M-CSF is an essential factor for osteoclast proliferation and differentiation, which is produced by osteoblasts in osseous tissue. Reaction of OPG with RANKL inhibits the binding of osteoclast precursors and osteoclasts to RANKL, therefore, OPG acts as a decoy receptor in the RANKL/RANK interaction. Blue structure: M-CSF (macrophage-colony stimulating factor), pink structure: M-CSF receptor (c-Fms), black structure: RANK (receptor activator of nuclear factor-κB), red structure: RANKL (RANK ligand), that is, osteoclast differentiation factor, orange structure: OPG (osteoprotegerin), that is, osteoclastogenesis inhibitory factor.