Tributyltin protects against ovariectomy-induced trabecular bone loss in C57BL/6J mice with an attenuated effect in high fat fed mice.
Tributyltin protects against ovariectomy-induced trabecular bone loss in C57BL/6J mice with an attenuated effect in high fat fed mice.
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DOI：
10.1016/j.taap.2021.115736
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发表时间：
2021-11-15
影响因子：
3.8
通讯作者：
Schlezinger JJ
中科院分区：
文献类型：
--
作者：
Freid R;Hussein AI;Schlezinger JJ
骨质不良的风险因素包括绝经期雌激素丢失、高脂肪饮食和暴露于激活过氧化物酶体增殖物激活受体γ（PPARγ）的药物/化学品。我们之前报道过，在体内，PPARγ和维甲酸X受体双重配体三丁基锡（TBT）抑制了骨膜骨形成，但增强了骨小梁形成。在这里，我们研究了饮食，卵巢切除术（OVX）和TBT暴露对骨结构的相互作用。C57 BL/6 J小鼠在10周龄时进行假手术或OVX。在12周龄时，将它们置于低（10%千卡）或高（45%千卡）脂肪、蔗糖匹配的饮食中，并用赋形剂或三丁基锡化合物（1或5毫克/千克）治疗14周。OVX增加了两种饮食小鼠的体重增加。三丁基锡化合物增加了喂食高脂肪饮食的完整小鼠的体重增加，但减少了OVX小鼠的体重增加。骨中元素锡浓度呈剂量依赖性增加。三丁基锡化合物对喂食两种食物的完整小鼠的皮质骨和骨小梁的影响都很小。无论饮食如何，OVX均导致皮质骨和松质骨减少。在高脂肪喂养的OVX小鼠中，三丁基锡化合物进一步降低了皮质厚度、骨面积和总面积。有趣的是，三丁基锡化合物在低脂肪喂养的小鼠中防止了卵巢切除引起的骨小梁丢失。TBT的保护作用被高脂所抵消。这些结果表明，三丁基锡化合物可以防止骨小梁丢失，即使在强吸收环境中，暴露水平甚至低于我们所显示的抑制稳态吸收。
Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We previously reported that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in vivo. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with vehicle or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed either diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat. These results show that TBT protects against trabecular bone loss, even in the presence of a strongly resorptive environment, at an even lower level of exposure than we showed repressed homeostatic resorption.
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影响因子：
4.1
作者：
Baroi S;Czernik PJ;Chougule A;Griffin PR;Lecka-Czernik B
通讯作者：
Lecka-Czernik B
影响因子：
3.7
作者：
Chen JR;Lazarenko OP;Wu X;Tong Y;Blackburn ML;Shankar K;Badger TM;Ronis MJ
通讯作者：
Ronis MJ
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
影响因子：
4.1
作者：
Baker, Amelia H.;Watt, James;Schlezinger, Jennifer J.
通讯作者：
Schlezinger, Jennifer J.
影响因子：
5.6
作者：
Halade, Ganesh V.;Rahman, Md M.;Williams, Paul J.;Fernandes, Gabriel
通讯作者：
Fernandes, Gabriel