Effects of arachidonic acid, docosahexaenoic acid, prostaglandin E2 and parathyroid hormone on osteoprotegerin and RANKL secretion by MOT3-E1 osteoblast-like cells

被引:47
作者
Coetzee, Magdalena
Haag, Marianne
Kruger, Marlena C.
机构
[1] Univ Pretoria, Dept Physiol, ZA-0001 Pretoria, South Africa
[2] Massey Univ, Inst Food Nutr & Human Hlth, Palmerston North 5301, New Zealand
基金
新加坡国家研究基金会;
关键词
arachidonic acid; docosahexaenoic acid; osteoprotegerin; RANKL; parathyroid hormone; osteoblasts;
D O I
10.1016/j.jnutbio.2006.03.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bone is continuously remodeled through resorption by osteoclasts and the subsequent synthesis of the bone matrix by osteoblasts. Cell-to-cell contact between osteoblasts and osteoclast precursors is required for osteoclast formation. RANKL (receptor activator of nuclear factor-kappa B ligand) expressed on osteoblastic cell membranes stimulates osteoclastogenesis, while osteoprotegerin (OPG) secreted by osteoblasts inhibits osteoclastogenesis. Although polyunsaturated fatty acids (PUFAs) have been implicated in bone homeostasis, the effects thereof on OPG and RANKL secretion have not been investigated. MC3T3-E1 osteoblasts were exposed to the n-6 PUFA arachidonic acid (AA) and the n-3 PUFA docosahexaenoic acid (DHA); furthermore, the bone-active hormone parathyroid hormone (PTH) and the effects thereof were tested on OPG and RANKL secretion. Prostaglandin E-2 (PGE(2)), a product of AA metabolism that was previously implicated in bone homeostasis, was included in the study. AA (5.0-20 mu g/ml) inhibited OPG secretion by 25-30%, which was attenuated by pretreatment with the cyclooxygenase blocker indomethacin, suggesting that the inhibitory effect of AA on OPG could possibly be PGE(2)-mediated. MC3T3-E1 cells secreted very low basal levels of RANKL, but AA stimulated RANKL secretion, thereby decreasing the OPG/ RANKL ratio. DHA suppressed OPG secretion to a smaller extent than AA. This could, however, be due to endogenous PGE(2) production. No RANKL could be detected after exposing the MC3T3-E1 cells to DHA, PTH did not affect OPG secretion, but stimulated RANKL secretion. This study demonstrates that AA and PTH reduce the OPG/RANKL ratio and may increase osteoclastogenesis. DHA, however, bad no significant effect on OPG or RANKL in this model. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:54 / 63
页数:10
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