Effects of 9cis,11trans and 10trans,12cis CLA on osteoclast formation and activity from human CD14+ monocytes

Ilana Platt,Ahmed El-Sohemy

doi:10.1186/1476-511x-8-15

Abstract

BackgroundMixed CLA isomers variably affect bone resorption in animals and decrease osteoclast formation and activity in murine osteoclasts. These variable effects may be due to the different isomers present in commercial preparations of CLA, and the effects of the predominant individual isomers, 9cis,11trans (9,11) and 10trans,12cis (10,12) CLA are not clear. The objectives of this study were to determine the effects of the individual CLA isomers on osteoclast formation and activity from human CD14+ monocytes, and to determine whether any changes are accompanied by changes in cathepsin K, matrix metalloproteinase-9 (MMP-9), receptor activator of NF-κB (RANK) and tumour necrosis factor alpha (TNFα) gene expression. Osteoclasts were identified as TRAP+ multinucleated cells. Osteoclast activity was quantified by the amount of TRAP in the cultured media.ResultsAt 50 μM, 9,11 CLA inhibited osteoclast formation by ~70%, and both 9,11 and 10,12 CLA decreased osteoclast activity by ~85–90%. Both isomers inhibited cathepsin K (50 μM 9,11 by ~60%; 10,12 by ~50%) and RANK (50 μM 9,11 by ~85%; 50 μM 10,12 by ~65%) expression, but had no effect on MMP-9 or TNFα expression.Conclusion9,11 CLA inhibits osteoclast formation and activity from human cells, suggesting that this isomer may prevent bone resorption in humans. Although 10,12 CLA did not significantly reduce osteoclast formation, it reduced osteoclast activity and cathepsin K and RANK expression, suggesting that this isomer may also affect bone resorption.

Highlights

Mixed conjugated linoleic acid (CLA) isomers variably affect bone resorption in animals and decrease osteoclast formation and activity in murine osteoclasts
The 9,11, but not 10,12, isomer of CLA has been shown to increase mineralized bone nodule formation from human osteoblast-like SaOS-2 cells [15]. These findings suggest that 9,11 CLA may affect bone resorption based on the knowledge that osteoblasts regulate osteoclast formation by altering the production of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) [17], and that CLA modulates RANKL signalling in murine osteoclasts in vitro [14]
The present study demonstrates that 9,11 CLA, the most abundant isomer found in food products from ruminant animals, inhibits osteoclast formation (TRAP+ multinucleated cells) from human CD14+ monocytes

Summary

Introduction

Mixed CLA isomers variably affect bone resorption in animals and decrease osteoclast formation and activity in murine osteoclasts. Dietary conjugated linoleic acid (CLA) has been reported to have inconsistent effects on bone mass [1,2,3,4,5,6,7,8,9,10,11,12,13] and on the differentiation and function of cultured bone cells [3,14,15,16] Of these studies, only a few have examined the effects of CLA on bone resorption in vivo [5,7,9,11,12,13] and on osteoclast formation and function in vitro [14]. The quantity of TRAP released into cell culture media correlates with bone resorption when osteoclasts are seeded onto bone slices [25]

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