title: Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells.
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.
authors: Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX, United States.
authors: Lee-Chuan C
authors: LC
authors: Yeh
authors: Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX, United States.
authors: Jeffery J
authors: JJ
authors: Ford
authors: Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX, United States; The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX, United States.
authors: John C
authors: JC
authors: Lee
authors: Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX, United States; The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX, United States. Electronic address: adamo@biochem.uthscsa.edu.
authors: Martin L
authors: ML
authors: Adamo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010168:Palmitates / Q000008:administration & dosage*; D051381:Rats; D012886:Skull / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*
chemical_list: D010168:Palmitates
keywords: Fetal rat calvarial cell culture; Lipotoxicity; Osteoblast differentiation; Palmitate