Abstract

An unbalanced diet can have adverse effects on health. Long chain polyunsaturated fatty acids (LCPUFAs) have been the focus of research owing to their necessity of inclusion in a healthy diet. However, the effects of LCPUFAs on human osteoclast formation and function have not been explored before. A human CD14+ monocyte differentiation model was used to elucidate the effects of an ω-3 LCPUFA, docosahexaenoic acid (DHA), and an ω-6 LCPUFA, arachidonic acid (AA), on osteoclast formation and activity. CD14+ monocytes were isolated from peripheral blood of healthy donors and stimulated with macrophage colony stimulating factor and receptor activator of nuclear factor kappa-B ligand to generate osteoclasts. Data from this study revealed that both the LCPUFAs decreased osteoclast formation potential of CD14+ monocytes in a dose-dependent manner when treated at an early stage of differentiation. Moreover, when exposed at a late stage of osteoclast differentiation AA and DHA impaired the bone resorptive potential of mature osteoclasts without affecting osteoclast numbers. AA and DHA abrogated vitronectin receptor expression in differentiating as well as mature osteoclasts. In contrast, the degree of inhibition for calcitonin receptor expression varied between the LCPUFAs with only AA causing inhibition during osteoclast differentiation. Furthermore, AA and DHA down regulated the expression of key osteoclast-specific genes in differentiating as well as mature osteoclasts. This study demonstrates for the first time that LCPUFAs can modulate osteoclast formation and function in a human primary osteoclast cell line.

Highlights

  • Bone is a dynamic tissue that is constantly remodelled by osteoclasts and osteoblasts

  • When mature osteoclasts were exposed to arachidonic acid (AA) at day 12 and analysed for enzymatic activity at day 15, the Long chain polyunsaturated fatty acids (LCPUFAs) at 40 μM and above potently exacerbated tartrate resistant acid phosphatase (TRAP) activity (Fig 1C)

  • To the best of our knowledge, this is the first report to study the effects of LCPUFAs on human CD14+ monocytes in differentiating and mature osteoclasts

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Summary

Introduction

Bone is a dynamic tissue that is constantly remodelled by osteoclasts and osteoblasts. Bone resorption by osteoclasts is usually followed by bone formation by osteoblasts in a balanced manner [1]. An imbalance in the process occurs during bone-related diseases such as osteoporosis, hypocalcaemia or osteopetrosis [1, 2]. Antiosteoclastogenic Effects of AA and DHA in Human CD14+ Monocytes

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