Regulation of osteoblast and adipocyte differentiation from human mesenchymal stem cells by conjugated linoleic acid.
Conjugated linoleic acid (CLA) describes a group of isomers of linoleic acid and has variable effects on bone formation and adiposity in vivo and in vitro. The variability may be due to individual effects of the predominant bioactive 9cis,11trans (9,11) and 10trans,12cis (10,12) CLA isomers. Osteoblasts and adipocytes are derived from mesenchymal stem cells (MSCs), and bone loss is accompanied by an increase in marrow adiposity. Osteoblast differentiation from MSCs requires activation of Wnt/beta-catenin signaling by Wnt10b, which inhibits adipocyte differentiation by suppressing CCAAT/enhancer-binding protein (C/EBP) alpha. The objective of this study was to determine if 9,11 and 10,12 CLA affect osteoblast and adipocyte differentiation from MSCs and to determine whether any effects are associated with changes in Wnt10b and C/EBPalpha expression. Osteoblast differentiation was assessed by calcium deposition, alkaline phosphatase (ALP) activity, and the expression of Wnt10b, runx2 and osteocalcin. Adipocyte differentiation was assessed by oil red O staining and C/EBPalpha, PPARgamma and FABP4 expression. Compared to vehicle, 9,11 CLA decreased calcium deposition ( approximately 15%), increased oil red O staining ( approximately 21-28%) and increased FABP4 (AP2) expression ( approximately 58-75%). In contrast, 10,12 CLA increased calcium deposition ( approximately 12-60%), ALP activity ( approximately 2.1-fold) and the expression of Wnt10b ( approximately 60-80%) and osteocalcin ( approximately 90%), but decreased oil red O staining ( approximately 30%) and the expression of C/EBPalpha ( approximately 24-38%) and PPARgamma ( approximately 60%) (P<.05). Thus, our findings demonstrate isomer-specific effects of CLA on MSC differentiation, and suggest that 10,12 CLA may be a useful therapeutic agent to promote osteoblast differentiation from MSCs.
Platt
Ilana D
ID
Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, Ontario, Canada, M5S 3E2.
El-Sohemy
Ahmed
A
D017667:Adipocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects*; D005260:Female; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology*; D013237:Stereoisomerism; D055815:Young Adult
C094849:10,12-octadecadienoic acid; D044243:Linoleic Acids, Conjugated; C046938:9,11-linoleic acid