Abstract
Because of its clinical relevance, extensive work has been performed to uncover the signaling pathways modulated by parathyroid hormone (PTH). This review focuses on the recent identification of novel effectors of the anabolic effect of PTH in bone. PTH-induced activation of PKA leads to inactivation of SIK2 and nuclear translocation of HDAC4/5. This inhibits MEF2C-dependent Sost expression. However, the phenotypic characterization of the HDAC4/5 double knockout mice shows normal anabolic response to intermittent PTH, supporting the notion that HDAC/Sost-independent mechanisms must exist. Lrp6 and a member of the Usp gene family have been identified as novel targets of the transcriptional coregulator Nascent polypeptide-associated complex And Coregulator alpha (αNAC) downstream from PTH activation. We propose that the αNAC cascade is involved in the transmission of the anabolic PTH signal. Further deciphering the signaling pathways transducing the anabolic effects of PTH will allow to develop novel therapeutically relevant molecules.
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