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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)176-183
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume474
DOIs
StatePublished - Oct 15 2018

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Ovariectomy
Protein Kinases
Bone
Bone and Bones
Knockout Mice
Osteoclasts
Bone Resorption
Thigh
Bone Density
Estrogens
Ablation
Surgery
Minerals
Serum

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

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title = "Protein kinase D1 conditional null mice show minimal bone loss following ovariectomy",
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)",
author = "Bollag, {Wendy B} and Kehong Ding and Vivek Choudhary and Jianrui Xu and Qing Zhong and Ranya Elsayed and Bailey, {Lakiea J.} and Elsalanty, {Mohammed Elsayed} and Kanglun Yu and Johnson, {Maribeth H} and {McGee Lawrence}, {Meghan Elizabeth} and Isales, {Carlos M}",
year = "2018",
month = "10",
day = "15",
doi = "10.1016/j.mce.2018.03.006",
language = "English (US)",
volume = "474",
pages = "176--183",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
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T1 - Protein kinase D1 conditional null mice show minimal bone loss following ovariectomy

AU - Bollag, Wendy B

AU - Ding, Kehong

AU - Choudhary, Vivek

AU - Xu, Jianrui

AU - Zhong, Qing

AU - Elsayed, Ranya

AU - Bailey, Lakiea J.

AU - Elsalanty, Mohammed Elsayed

AU - Yu, Kanglun

AU - Johnson, Maribeth H

AU - McGee Lawrence, Meghan Elizabeth

AU - Isales, Carlos M

PY - 2018/10/15

Y1 - 2018/10/15

N2 - 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.

AB - 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.

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