Effects of arachidonic acid, docosahexaenoic acid, prostaglandin E2 and parathyroid hormone on osteoprotegerin and RANKL secretion by MOT3-E1 osteoblast-like cells
Effects of arachidonic acid, docosahexaenoic acid, prostaglandin E2 and parathyroid hormone on osteoprotegerin and RANKL secretion by MOT3-E1 osteoblast-like cells
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DOI：
10.1016/j.jnutbio.2006.03.002
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发表时间：
2007-01-01
影响因子：
5.6
通讯作者：
Kruger, Marlena C.
中科院分区：
文献类型：
--
作者：
Coetzee, Magdalena;Haag, Marianne;Kruger, Marlena C.
骨通过破骨细胞的再吸收和随后的成骨细胞合成骨基质而不断重塑。破骨细胞的形成需要成骨细胞和破骨细胞前体之间的细胞与细胞接触。成骨细胞膜上表达的RANKL（核因子-κ B配体的受体激活剂）刺激破骨细胞生成，而成骨细胞分泌的骨保护素（OPG）抑制破骨细胞生成。尽管多不饱和脂肪酸（PUFA）与骨稳态有关，但尚未研究其对OPG和RANKL分泌的影响。将MC 3 T3-E1成骨细胞暴露于n-6 PUFA花生四烯酸（AA）和n-3 PUFA二十二碳六烯酸（DHA）中，并检测骨活性激素甲状旁腺激素（PTH）及其对OPG和RANKL分泌的影响。前列腺素E-2（PGE（2））是AA代谢的产物，以前与骨稳态有关，被纳入研究。AA（5.0-20 μ g/ml）抑制OPG分泌25- 30%，用环氧化酶阻断剂吲哚美辛预处理可减弱这种抑制作用，提示AA对OPG的抑制作用可能是PGE（2）介导的。MC 3 T3-E1细胞分泌非常低水平的RANKL，但AA刺激RANKL分泌，从而降低OPG/ RANKL比值。DHA抑制OPG分泌的程度小于AA。然而，这可能是由于内源性PGE（2）的产生。DHA作用于MC 3 T3-E1细胞后，未检测到RANKL的表达，PTH不影响OPG的分泌，但刺激RANKL的分泌。这项研究表明，AA和PTH降低OPG/RANKL比值，并可能增加破骨细胞生成。DHA对OPG和RANKL无明显影响。(c)2007年爱思唯尔公司All rights reserved.
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.