[Hormones and osteoporosis update. Mechanisms of anabolic and catabolic effects of PTH on bone].
Treatment of osteoporosis aims to increase bone mass by suppressing bone resorption and/or stimulating bone formation. Among drugs clinically available for treatment of osteoporosis, only PTH stimulates bone formation. However, the mechanism by which PTH promotes bone formation is not clearly understood. PTH signaling in osteoblasts increases osteoblast progenitors. It appears that this effect of PTH is exerted mainly through multiple indirect pathways. Among them, the Wnt signaling pathway is of particular interest because of the strong human genetic evidence that Wnt signaling positively regulates bone mass. Activation of the PTH receptor increases Wnt signaling by down-regulating expression of Dkk1 and sclerostin, endogenous inhibitors for Wnt signaling, and by directly activating LRP6, a Wnt co-receptor. Understanding the mechanisms of the anabolic effect of PTH may lead to development of novel drugs to stimulate bone formation.
Kobayashi
Tatsuya
T
Endocrine Unit, Massachusetts General Hospital, USA.
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D015536:Down-Regulation; D015195:Drug Design; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology*; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000502:physiology; D011973:Receptors, LDL / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D051153:Wnt Proteins / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; D011973:Receptors, LDL; C422903:SOST protein, human; D051153:Wnt Proteins