Parathyroid hormone inhibits Notch signaling in osteoblasts and osteocytes

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  5. Parathyroid hormone inhibits Notch signaling in osteoblasts and osteocytes

Bone. 2017 Oct;103:159-167. doi: 10.1016/j.bone.2017.06.027

Parathyroid hormone (PTH) and Notch receptors regulate bone formation by governing the function of osteoblastic cells. To determine whether PTH interacts with Notch signaling as a way to control osteoblast function, we tested the effects of PTH on Notch activity in osteoblast- and osteocyte-enriched cultures.

Induction of Notch signaling in osteocytes did not alter the inhibitory effect of PTH on Sost expression, but reduced the stimulation of Tnfsf11 mRNA levels by PTH. In agreement with these in vitro observations, male mice administered with PTH displayed suppressed Hey1 and HeyL expression in parietal bones. Transactivation experiments with a Notch reporter construct and electrophoretic mobility shift assays in osteoblast-enriched cells suggest that PTH acts by decreasing the capacity of Rbpjκ to bind to DNA. In conclusion, downregulation of Notch in osteoblasts and osteocytes may represent a mechanism contributing to the anabolic effects of PTH in bone.

Zanotti S, Canalis E

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Laboratorios Rubió
Grupo Italfármaco
Gedeon Richter
Kyowa Kirin
Meiji Pharma
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