The cell biology of parathyroid hormone in osteoblasts.
Continuous exposure to parathyroid hormone (PTH) is associated with catabolic effects, whereas intermittent exposure to low doses of PTH is associated with anabolic effects. By controlling osteoblast function, PTH increases bone formation on cancellous, endocortical, and periosteal bone surfaces. In general, PTH does not affect the replication of uncommitted osteoblast progenitors but suppresses proliferation of committed osteoprogenitors. Intermittent PTH promotes osteoblast differentiation, in part, by its ability to promote exit from the cell cycle, to activate Wnt signaling in osteoblasts, and to inhibit the Wnt antagonist sclerostin in osteocytes. Insulin-like growth factor-1 is also required for the actions of PTH to increase osteoblast numbers. Intermittent PTH prolongs osteoblast survival in rodents by mechanisms that involve activation and proteolytic degradation of Runx2. PTH's ability to orchestrate a dynamic range of signaling cascades that determine osteoblast fate may explain both its catabolic and beneficial actions on the skeleton.
Kousteni
Stavroula
S
Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Bilezikian
John P
JP
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D010281:Parathyroid Hormone / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology
D010281:Parathyroid Hormone; D051153:Wnt Proteins; D007334:Insulin-Like Growth Factor I
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