Regulation of osteoblast and adipocyte differentiation from human mesenchymal stem cells by conjugated linoleic acid

Abstract

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 9 cis,11 trans (9,11) and 10 trans,12 cis (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/β-catenin signaling by Wnt10b, which inhibits adipocyte differentiation by suppressing CCAAT/enhancer-binding protein (C/EBP) α. 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/EBPα 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/EBPα, PPARγ and FABP4 expression. Compared to vehicle, 9,11 CLA decreased calcium deposition (∼15%), increased oil red O staining (∼21-28%) and increased FABP4 (AP2) expression (∼58-75%). In contrast, 10,12 CLA increased calcium deposition (∼12-60%), ALP activity (∼2.1-fold) and the expression of Wnt10b (∼60-80%) and osteocalcin (∼90%), but decreased oil red O staining (∼30%) and the expression of C/EBPα (∼24-38%) and PPARγ (∼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.