Parathyroid hormone signaling in bone and kidney

Parathyroid hormone (PTH) maintains a physiological balance of calcium and phosphate concentrations by binding to its receptor on the plasma membrane of cells in bone and kidney. It signals through multiple pathways, including protein kinase A and protein kinase C, although a preference for certain pathways is apparent in each organ and function. Here, we will review the recent advancements regarding PTH signaling in bone and kidney.

Wnt proteins have been reported as important regulators of bone metabolism in both PTH-dependent and independent pathways. Recent studies emphasize its role as a mediator of PTH signaling, as PTH treatment increased the expression of wnt4 and sfrp4 and decreased the expression of Wnt inhibitors such as Sost and sclerostin, leading to an increase in Wnt signaling. In kidney, sodium-hydrogen exchanger regulatory factor 1, originally known for its role in the retention of NaPi-IIa at the apical membrane, was shown to have multiple roles in PTH signaling, both as a mediator and regulator.

PTH activates a number of different signaling pathways by binding to a single receptor in bone and kidney. Recent studies demonstrate the involvement of novel factors as well as additional roles for previously identified downstream factors of PTH.