PTH/PTHrP Receptor in Early Development and Indian Hedgehog—Regulated Bone Growth

TLDR

The PTH/PTHrP receptor binds the calcium‑regulating hormone PTH and the paracrine factor PTHrP, each of which can activate multiple receptor isoforms. The receptor’s role was examined by generating mice lacking the PTH/PTHrP receptor gene via homologous recombination. Loss of the receptor causes mid‑gestation lethality and, in survivors, accelerated chondrocyte differentiation and bone resistance to PTHrP and Sonic hedgehog, indicating that the receptor mediates Indian Hedgehog and PTHrP signaling in chondrocyte maturation.

Abstract

The PTH/PTHrP receptor binds to two ligands with distinct functions: the calcium-regulating hormone, parathyroid hormone (PTH), and the paracrine factor, PTH-related protein (PTHrP). Each ligand, in turn, is likely to activate more than one receptor. The functions of the PTH/PTHrP receptor were investigated by deletion of the murine gene by homologous recombination. Most PTH/PTHrP receptor (−/−) mutant mice died in mid-gestation, a phenotype not observed in PTHrP (−/−) mice, perhaps because of the effects of maternal PTHrP. Mice that survived exhibited accelerated differentiation of chondrocytes in bone, and their bones, grown in explant culture, were resistant to the effects of PTHrP and Sonic hedgehog. These results suggest that the PTH/PTHrP receptor mediates the effects of Indian Hedgehog and PTHrP on chondrocyte differentiation.