Cells of bone Within the skeleton there are 4 basic types of bone cells; osteoclasts, osteoblast, bone lining cells and osteocytes. Osteoclasts (Figure 1.2A) are multinucleated cells derived from monocytes that are ultimately from HSCs first discovered in 1873 by Kolliker. Osteoclast maturation requires the presence of receptor activator of nuclear factor κβ ligand (RANKL) and Macrophage colony-stimulating factor (M-CSF) (, , ). Overexpression of osteoprotegerin (OPG), soluble receptor that competes with RANK for RANKL, reduces osteoclastogenesis in mice. On the other hand, lack of OPG has been shown to accelerate osteoclastogenesis and OPG Ko mice (OPG−/− develop mice) severe osteoporosis (). Osteoclasts form at skeletal sites, in which stromal cells and osteoblasts express RANKL and M-CSF and it is the interaction of these ligands with their receptors on monocyte/macrophage cells that induce commitment to the osteoclast phenotype. Osteoclasts have a critical role in the regulation of bone formation and regulation of bone mass, in which mature and active osteoclasts are responsible for resorbing mineralized bone matrix and breaking up the organic bone (90% collagen). Differentiated osteoclasts express integrin, which binds to bone matrix via αvβ3 proteins leading to the formation of sealed pocket for the secretion of cathepsin K, the major protease involved in the degradation of type I collagen (, ). After attachment, osteoclasts exhibit a highly polarized cytoplasmic organization. The
Cells of bone Within the skeleton there are 4 basic types of bone cells; osteoclasts, osteoblast, bone lining cells and osteocytes. Osteoclasts (Figure 1.2A) are multinucleated cells derived from monocytes that are ultimately from HSCs first discovered in 1873 by Kolliker. Osteoclast maturation requires the presence of receptor activator of nuclear factor κβ ligand (RANKL) and Macrophage colony-stimulating factor (M-CSF) (, , ). Overexpression of osteoprotegerin (OPG), soluble receptor that competes with RANK for RANKL, reduces osteoclastogenesis in mice. On the other hand, lack of OPG has been shown to accelerate osteoclastogenesis and OPG Ko mice (OPG−/− mice) develop severe osteoporosis (). Osteoclasts form at skeletal sites, in which stromal cells and osteoblasts express RANKL and M-CSF and it is the interaction of these ligands with their receptors on monocyte/macrophage cells that induce commitment to the osteoclast phenotype. Osteoclasts have a critical role in the regulation of bone formation and regulation of bone mass, in which mature and active osteoclasts are responsible for resorbing mineralized bone matrix and breaking up the organic bone (90% collagen). Differentiated osteoclasts express αvβ3 integrin, which binds to bone matrix via proteins leading to the formation of sealed pocket for the secretion of cathepsin K, the major protease involved in the degradation of type I collagen (, ). After attachment, osteoclasts exhibit a highly polarized cytoplasmic organization. The
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