Protein kinase D1 conditional null mice show minimal bone loss following ovariectomy

Mol Cell Endocrinol. 2018 Oct 15:474:176-183. doi: 10.1016/j.mce.2018.03.006. Epub 2018 Mar 9.

Abstract

We previously found that 3- and 6-month-old male mice with conditional ablation of protein kinase D1 (PRKD1) in osteoprogenitor cells (expressing Osterix) exhibited reduced bone mass. Others have demonstrated similar effects in young female PRKD1-deficient mice. Here we examined the bone resorptive response of adult female floxed control and conditional knockout (cKO) mice undergoing sham surgery or ovariectomy (OVX). Femoral and tibial bone mineral density (BMD) values were significantly reduced upon OVX in control, but not cKO, females compared to the respective sham-operated mice. Micro-CT analysis showed that OVX significantly increased trabecular number and decreased trabecular spacing in cKO but not control mice. Finally, in control mice serum levels of a marker of bone resorption (pyridinoline crosslinks) and the osteoclast activator RANKL significantly increased upon OVX; however, no such OVX-induced increase was observed in cKO mice. Our results suggest the potential importance of PRKD1 in response to estrogen loss in bone.

Keywords: Bone mass; Osteopenia; Osteoporosis; Protein kinase D1 (PRKD1); Pyridinoline crosslinks (PYD); Receptor activator of nuclear factor kappa-B ligand (RANKL).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / blood
  • Animals
  • Bone Density
  • Bone Resorption / blood
  • Bone Resorption / enzymology*
  • Bone Resorption / etiology*
  • Bone Resorption / pathology
  • Bone and Bones / pathology
  • Female
  • Mice, Knockout
  • Minerals / metabolism
  • Organ Size
  • Osteoprotegerin / metabolism
  • Ovariectomy*
  • Protein Kinase C / deficiency*
  • Protein Kinase C / metabolism
  • RANK Ligand / blood
  • Stem Cells / metabolism
  • Tartrate-Resistant Acid Phosphatase / metabolism

Substances

  • Amino Acids
  • Minerals
  • Osteoprotegerin
  • RANK Ligand
  • pyridinoline
  • protein kinase D
  • Protein Kinase C
  • Tartrate-Resistant Acid Phosphatase