skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells

Abstract

Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ inmore » FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects.« less

Authors:
;  [1];  [1]
  1. Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States)
Publication Date:
OSTI Identifier:
22416656
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGING; ALKALINE PHOSPHATASE; APOPTOSIS; BONE MARROW; CARBOXYLASE; CARBOXYLIC ACIDS; CELL PROLIFERATION; CONNECTIVE TISSUE CELLS; LIPIDS; MESSENGER-RNA; MINERALIZATION; OSTEOPOROSIS; OXIDATION; RATS; SKELETON

Citation Formats

Yeh, Lee-Chuan C., Ford, Jeffery J., Lee, John C., The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX, Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu, and The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.06.063.
Yeh, Lee-Chuan C., Ford, Jeffery J., Lee, John C., The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX, Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu, & The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells. United States. https://doi.org/10.1016/J.BBRC.2014.06.063
Yeh, Lee-Chuan C., Ford, Jeffery J., Lee, John C., The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX, Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu, and The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX. 2014. "Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells". United States. https://doi.org/10.1016/J.BBRC.2014.06.063.
@article{osti_22416656,
title = {Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells},
author = {Yeh, Lee-Chuan C. and Ford, Jeffery J. and Lee, John C. and The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX and Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu and The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX},
abstractNote = {Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects.},
doi = {10.1016/J.BBRC.2014.06.063},
url = {https://www.osti.gov/biblio/22416656}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 450,
place = {United States},
year = {Fri Jul 18 00:00:00 EDT 2014},
month = {Fri Jul 18 00:00:00 EDT 2014}
}