title: Cell Death in Chondrocytes, Osteoblasts, and Osteocytes.
abstract: Cell death in skeletal component cells, including chondrocytes, osteoblasts, and osteocytes, plays roles in skeletal development, maintenance, and repair as well as in the pathogenesis of osteoarthritis and osteoporosis. Chondrocyte proliferation, differentiation, and apoptosis are important steps for endochondral ossification. Although the inactivation ofP53andRBis involved in the pathogenesis of osteosarcomas, the deletion ofp53and inactivation of Rb are insufficient to enhance chondrocyte proliferation, indicating the presence of multiple inhibitory mechanisms against sarcomagenesis in chondrocytes. The inflammatory processes induced by mechanical injury and chondrocyte death through the release of danger-associated molecular patterns (DAMPs) are involved in the pathogenesis of posttraumatic osteoarthritis. The overexpression ofBCLXLincreases bone volume with a normal structure and maintains bone during aging by inhibiting osteoblast apoptosis. p53 inhibits osteoblast proliferation and enhances osteoblast apoptosis, thereby reducing bone formation, but also exerts positive effects on osteoblast differentiation through the Akt-FoxOs pathway. Apoptotic osteocytes release ATP, which induces the receptor activator of nuclear factor κ-B ligand (Rankl) expression and osteoclastogenesis, from pannexin 1 channels. Osteocyte death ultimately results in necrosis; DAMPs are released to the bone surface and promote the production of proinflammatory cytokines, which induce Rankl expression, and osteoclastogenesis is further enhanced.
authors.affiliation: Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan. komorit@nagasaki-u.ac.jp.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
mesh_terms: D000067531:Alarmins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*
chemical_list: D000067531:Alarmins
keywords: ATP; BCLXL; DAMPs; FoxO; Rankl; Rb; apoptosis; necrosis; osteoarthritis; p53