The newly formed osteoclast must be activated to become a bone-resorbing cell. During this process, it becomes highly polarized. When actively resorbing bone, osteoclasts exhibit three specialized regions:  The ruffled border is the part of the cell in direct contact with bone. It contains numerous deep plasma membrane infoldings forming microvillous-type structures responsible for increasing surface area for the exocytosis of hydrolytic enzymes and secretion of protons by ATP–dependent proton pumps, as well as endocytosis of degradation products and bone debris. The ruffled border stains less intensely than the remainder of the cell and often appears as a light band adjacent to the bone at
FIGURE 8.12 • Photomicrograph of an osteoclast on a bone spicule. This Mallory-stained specimen shows a spicule made of calcified cartilage (stained light blue) and a covering of bone tissue (stained dark blue). An osteoclast on the left side of the spicule has resorbed bone tissue and lies in a depression (Howship’s lacuna) in the spicule. The light band between the osteoclast and the bone spicule corresponds to the ruffled border of the osteoclast. The arrows on the nongrowing surface indicate cytoplasm of inactive bone-lining cells (osteoprogenitor cells). In contrast, bone is being deposited on the opposite side of the spicule, as evidenced by the presence of osteoblasts on this surface and newly formed osteocytes just below the surface of the spicule. 550.
common myeloid progenitor (CMP, CFU-GEMM) granulocyte/ monocyte progenitors (GMP, CFU-GM)
FIGURE 8.13 • The origin of osteoclasts. Osteoclasts are derived from fusion of granulocyte/monocyte progenitor cells (GMP, CFUGM), which originate from multipotential common myeloid progenitor cells (CMP, CFU-GEMM). GMP cells also give rise to the granulocyte and monocyte cell lineages such as neutrophil progenitor (NoP, CFU-G) and monocyte progenitor (MoP, CFU-M) cells. Osteoclast formation occurs in close association with stromal cells in bone marrow, which secrete monocyte colony-stimulating factor (M-CSF ), tumor necrosis factor (TNF ), and several interleukins (ILs). Osteoclast precursors express c-fos and NFB, and receptor molecules called RANK (receptor activator of nuclear factor  B). The signal generated by the interaction of the RANK receptor with the RANK ligand (RANKL) molecule is essential for osteoclast differentiation and maturation. During inflammation, T lymphocytes produce both soluble and membrane-bound RANKL molecules, which increase bone resorption. These pathways can be blocked by osteoprotegerin (OPG). Note that activated T lymphocytes can stimulate formation of osteoclasts by producing both membrane-bound and soluble RANKL molecules.