Phospholipase C signaling via the parathyroid hormone (PTH)/PTH-related peptide receptor is essential for normal bone responses to PTH

Endocrinology. 2010 Aug;151(8):3502-13. doi: 10.1210/en.2009-1494. Epub 2010 May 25.


We have previously shown that differentiation of hypertrophic chondrocytes is delayed in mice expressing a mutated PTH/PTHrP receptor (PTHR) (called DSEL here) that stimulates adenylyl cyclase normally but fails to activate phospholipase C (PLC). To better understand the role of PLC signaling via the PTHR in skeletal and mineral homeostasis, we examined these mice fed a normal or calcium-deficient diet. On a standard diet, DSEL mice displayed a modest decrease in bone mass. Remarkably, when fed a low-calcium diet or infused with PTH, DSEL mice exhibited strikingly curtailed peritrabecular stromal cell responses and attenuated new bone formation when compared with Wt mice. Attenuated in vitro colony formation was also observed in bone marrow cells derived from DSEL mice fed a low-calcium diet. Furthermore, PTH stimulated proliferation and increased mRNAs encoding cyclin D1 in primary osteoblasts derived from Wt but not from DSEL mice. Our data indicate that PLC signaling through the PTHR is required for skeletal homeostasis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Bone Remodeling / drug effects
  • Bone Remodeling / genetics
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Bone and Bones / physiology
  • Calcium, Dietary / pharmacology
  • Cells, Cultured
  • Diet
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoblasts / physiology
  • Parathyroid Hormone / metabolism
  • Parathyroid Hormone / pharmacology*
  • Receptor, Parathyroid Hormone, Type 1 / genetics
  • Receptor, Parathyroid Hormone, Type 1 / metabolism
  • Receptor, Parathyroid Hormone, Type 1 / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Type C Phospholipases / metabolism
  • Type C Phospholipases / physiology*


  • Calcium, Dietary
  • Parathyroid Hormone
  • Receptor, Parathyroid Hormone, Type 1
  • Type C Phospholipases