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/EBP alpha 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/EBP alpha, PPAR gamma and FABP4 expression. Compared to vehicle, 9,11 CLA decreased calcium deposition (similar to 15%), increased oil red O staining (similar to 21-28%) and increased FABP4 (AP2) expression (similar to 58-75%). In contrast, 10,12 CLA increased calcium deposition (similar to 12-60%), ALP activity (similar to 2.1-fold) and the expression of Wnt10b (similar to 60-80%) and osteocalcin (similar to 90%), but decreased oil red O staining (similar to 30%) and the expression of C/EBP alpha (similar to 24-38%) and PPAR gamma (similar to 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. (C) 2009 Elsevier Inc. All rights reserved.