Deletion of protein kinase D1 in osteoprogenitor cells results in decreased osteogenesis in vitro and reduced bone mineral density in vivo

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Abstract

Protein kinase D1 (PRKD1) is thought to play a role in a number of cellular functions, including proliferation and differentiation. We hypothesized that PRKD1 in bone marrow-derived mesenchymal stem cells (BMMSC) could modulate osteogenesis. In BMMSCs from floxed PRKD1 mice, PRKD1 ablation with adenovirus-mediated Cre-recombinase expression inhibited BMMSC differentiation in vitro. In 3- and 6-month-old conditional knockout mice (cKO), in which PRKD1 was ablated in osteoprogenitor cells by osterix promoter-driven Cre-recombinase, bone mineral density (BMD) was significantly reduced compared with floxed control littermates. Microcomputed tomography analysis also demonstrated a decrease in trabecular thickness and bone volume fraction in cKO mice at these ages. Dynamic bone histomorphometry suggested a mineralization defect in the cKO mice. However, by 9 months of age, the bone appeared to compensate for the lack of PRKD1, and BMD was not different. Taken together, these results suggest a potentially important role for PRKD1 in bone formation.

Original languageEnglish (US)
Pages (from-to)22-31
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume461
DOIs
StatePublished - Feb 5 2018

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Osteogenesis
Bone Density
Protein Kinases
Minerals
Bone
Knockout Mice
Mesenchymal Stromal Cells
Stem cells
Bone Marrow
Bone and Bones
X-Ray Microtomography
Adenoviridae
In Vitro Techniques
Cell Differentiation
Ablation
Tomography
Volume fraction
Proteins
Defects

Keywords

  • Bone
  • Mesenchymal stem cells
  • Mineralization
  • Osteoprogenitor
  • Osterix
  • Protein kinase D1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

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title = "Deletion of protein kinase D1 in osteoprogenitor cells results in decreased osteogenesis in vitro and reduced bone mineral density in vivo",
abstract = "Protein kinase D1 (PRKD1) is thought to play a role in a number of cellular functions, including proliferation and differentiation. We hypothesized that PRKD1 in bone marrow-derived mesenchymal stem cells (BMMSC) could modulate osteogenesis. In BMMSCs from floxed PRKD1 mice, PRKD1 ablation with adenovirus-mediated Cre-recombinase expression inhibited BMMSC differentiation in vitro. In 3- and 6-month-old conditional knockout mice (cKO), in which PRKD1 was ablated in osteoprogenitor cells by osterix promoter-driven Cre-recombinase, bone mineral density (BMD) was significantly reduced compared with floxed control littermates. Microcomputed tomography analysis also demonstrated a decrease in trabecular thickness and bone volume fraction in cKO mice at these ages. Dynamic bone histomorphometry suggested a mineralization defect in the cKO mice. However, by 9 months of age, the bone appeared to compensate for the lack of PRKD1, and BMD was not different. Taken together, these results suggest a potentially important role for PRKD1 in bone formation.",
keywords = "Bone, Mesenchymal stem cells, Mineralization, Osteoprogenitor, Osterix, Protein kinase D1",
author = "Bollag, {Wendy B} and Vivek Choudhary and Qing Zhong and Kehong Ding and Jianrui Xu and Ranya Elsayed and Kanglun Yu and Yun Su and Bailey, {Lakiea J.} and Shi, {Xing Ming} and Elsalanty, {Mohammed Elsayed} and Johnson, {Maribeth H} and {McGee Lawrence}, {Meghan Elizabeth} and Isales, {Carlos M}",
year = "2018",
month = "2",
day = "5",
doi = "10.1016/j.mce.2017.08.005",
language = "English (US)",
volume = "461",
pages = "22--31",
journal = "Molecular and Cellular Endocrinology",
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publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Deletion of protein kinase D1 in osteoprogenitor cells results in decreased osteogenesis in vitro and reduced bone mineral density in vivo

AU - Bollag, Wendy B

AU - Choudhary, Vivek

AU - Zhong, Qing

AU - Ding, Kehong

AU - Xu, Jianrui

AU - Elsayed, Ranya

AU - Yu, Kanglun

AU - Su, Yun

AU - Bailey, Lakiea J.

AU - Shi, Xing Ming

AU - Elsalanty, Mohammed Elsayed

AU - Johnson, Maribeth H

AU - McGee Lawrence, Meghan Elizabeth

AU - Isales, Carlos M

PY - 2018/2/5

Y1 - 2018/2/5

N2 - Protein kinase D1 (PRKD1) is thought to play a role in a number of cellular functions, including proliferation and differentiation. We hypothesized that PRKD1 in bone marrow-derived mesenchymal stem cells (BMMSC) could modulate osteogenesis. In BMMSCs from floxed PRKD1 mice, PRKD1 ablation with adenovirus-mediated Cre-recombinase expression inhibited BMMSC differentiation in vitro. In 3- and 6-month-old conditional knockout mice (cKO), in which PRKD1 was ablated in osteoprogenitor cells by osterix promoter-driven Cre-recombinase, bone mineral density (BMD) was significantly reduced compared with floxed control littermates. Microcomputed tomography analysis also demonstrated a decrease in trabecular thickness and bone volume fraction in cKO mice at these ages. Dynamic bone histomorphometry suggested a mineralization defect in the cKO mice. However, by 9 months of age, the bone appeared to compensate for the lack of PRKD1, and BMD was not different. Taken together, these results suggest a potentially important role for PRKD1 in bone formation.

AB - Protein kinase D1 (PRKD1) is thought to play a role in a number of cellular functions, including proliferation and differentiation. We hypothesized that PRKD1 in bone marrow-derived mesenchymal stem cells (BMMSC) could modulate osteogenesis. In BMMSCs from floxed PRKD1 mice, PRKD1 ablation with adenovirus-mediated Cre-recombinase expression inhibited BMMSC differentiation in vitro. In 3- and 6-month-old conditional knockout mice (cKO), in which PRKD1 was ablated in osteoprogenitor cells by osterix promoter-driven Cre-recombinase, bone mineral density (BMD) was significantly reduced compared with floxed control littermates. Microcomputed tomography analysis also demonstrated a decrease in trabecular thickness and bone volume fraction in cKO mice at these ages. Dynamic bone histomorphometry suggested a mineralization defect in the cKO mice. However, by 9 months of age, the bone appeared to compensate for the lack of PRKD1, and BMD was not different. Taken together, these results suggest a potentially important role for PRKD1 in bone formation.

KW - Bone

KW - Mesenchymal stem cells

KW - Mineralization

KW - Osteoprogenitor

KW - Osterix

KW - Protein kinase D1

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