The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats.
The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats.
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过氧化物酶体增殖物激活的受体（PPAR）α激动剂非诺贝特保持骨骼量，而PPARγγ激动剂Pioglitazone在卵巢切除的大鼠中夸大了骨质流失。
DOI：
10.1186/1472-6823-11-11
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发表时间：
2011-05-26
影响因子：
2.7
通讯作者：
Syversen U
中科院分区：
文献类型：
--
作者：
Stunes AK;Westbroek I;Gustafsson BI;Fossmark R;Waarsing JH;Eriksen EF;Petzold C;Reseland JE;Syversen U
过氧化物酶体增殖物激活受体（PPAR）γ的激活与骨丢失和骨折风险增加有关，而PPARalpha的激活似乎具有积极的骨骼效应。为了进一步探索这些作用，我们检测了PPARalpha激动剂非诺贝特和Wyeth 14643以及PPARgamma激动剂吡格列酮对卵巢切除大鼠的骨矿物质密度（BMD）、骨结构和生物力学强度的作用。将55只雌性Sprague-Dawley大鼠分为5组。一组为假手术组，给予溶媒（甲基纤维素），其他组切除卵巢，分别给予溶媒、非诺贝特、Wyeth 14643和吡格列酮，每日一次，持续4个月。采用双能X线骨密度仪（DXA）测量全身和股骨BMD，并进行股骨生物力学测试和股骨干和股骨头的显微计算机断层扫描（microCT）。与卵巢切除对照组相比，假手术对照组和给予非诺贝特的卵巢切除动物的全身和股骨BMD显著较高。给予Wyeth 14643的卵巢切除大鼠的全身BMD维持在假手术水平，而与假手术和卵巢切除对照组相比，吡格列酮组大鼠的全身和股骨BMD较低，骨质量受损，机械强度较低。相比之下，给予非诺贝特的大鼠皮质体积、骨小梁体积和厚度以及皮质内体积维持在假手术水平。在卵巢切除大鼠中，PPARalpha激动剂非诺贝特和较小程度的PPARaplha激动剂Wyeth 14643将BMD和骨结构维持在假手术水平，而PPARgamma激动剂吡格列酮加剧了骨丢失并对骨结构产生负面影响。
Activation of peroxisome proliferator-activated receptor (PPAR)gamma is associated with bone loss and increased fracture risk, while PPARalpha activation seems to have positive skeletal effects. To further explore these effects we have examined the effect of the PPARalpha agonists fenofibrate and Wyeth 14643, and the PPARgamma agonist pioglitazone, on bone mineral density (BMD), bone architecture and biomechanical strength in ovariectomized rats. Fifty-five female Sprague-Dawley rats were assigned to five groups. One group was sham-operated and given vehicle (methylcellulose), the other groups were ovariectomized and given vehicle, fenofibrate, Wyeth 14643 and pioglitazone, respectively, daily for four months. Whole body and femoral BMD were measured by dual X-ray absorptiometry (DXA), and biomechanical testing of femurs, and micro-computed tomography (microCT) of the femoral shaft and head, were performed. Whole body and femoral BMD were significantly higher in sham controls and ovariectomized animals given fenofibrate, compared to ovariectomized controls. Ovariectomized rats given Wyeth 14643, maintained whole body BMD at sham levels, while rats on pioglitazone had lower whole body and femoral BMD, impaired bone quality and less mechanical strength compared to sham and ovariectomized controls. In contrast, cortical volume, trabecular bone volume and thickness, and endocortical volume were maintained at sham levels in rats given fenofibrate. The PPARalpha agonist fenofibrate, and to a lesser extent the PPARaplha agonist Wyeth 14643, maintained BMD and bone architecture at sham levels, while the PPARgamma agonist pioglitazone exaggerated bone loss and negatively affected bone architecture, in ovariectomized rats.
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影响因子：
4.8
作者：
Ali, AA;Weinstein, RS;Jilka, RL
通讯作者：
Jilka, RL
影响因子：
3.2
作者：
Derosa, Giuseppe;Cicero, Arrigo F. G.;Ragonesi, Pietro D.
通讯作者：
Ragonesi, Pietro D.
影响因子：
--
作者：
Hasegawa, Takuro;Oizumi, Kiyoshi;Aubin, Jane E.
通讯作者：
Aubin, Jane E.
影响因子：
5.8
作者：
Boutroy, S;Bouxsein, ML;Delmas, PD
通讯作者：
Delmas, PD
影响因子：
3.5
作者：
Jackson, SM;Demer, LL
通讯作者：
Demer, LL