Targeting the lateral but not the third ventricle induces bone loss in ewe: An experimental approach to generate an improved large animal model of osteoporosis
Targeting the lateral but not the third ventricle induces bone loss in ewe: An experimental approach to generate an improved large animal model of osteoporosis
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针对侧脑室而不是第三脑室会导致母羊骨质流失：一种改进的大型动物骨质疏松模型的实验方法
DOI：
10.1097/ta.0b013e318238b3bd
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Pogoda P
中科院分区：
文献类型：
--
作者：
Oheim R;Beil FT;Barvencik F;Egermann M;Amling M;Clarke IJ;Pogoda P
背景：骨质疏松症是一种以骨丢失和骨骼脆性增加为特征的慢性疾病。新的治疗方法的临床前测试需要大型动物模型。我们最近已经证明，持续脑室内（ICV）应用瘦素进入侧脑室（LV）诱导母羊骨丢失。根据这些发现，我们推断第三脑室（TV）是一个更好的靶点，因为其位置更靠近下丘脑，下丘脑介导瘦素对骨的影响。方法：将Corriedale绵羊随机分为四组，每组四只母羊：对照组（control），卵巢切除加ICV应用脑脊液（OVX），OVX加ICV应用瘦素进入LV（瘦素-LV）;和将瘦素ICV应用于TV（瘦素-TV）。3个月后，组织形态计量学特征和骨转换参数进行了analysed.Results：高度显着的骨小梁丢失，观察只有瘦素LV组。OVX组和Leptin-TV组破骨细胞指数和尿交叉排尿量增加。与此相反，血清成骨细胞活性的参数只有瘦素LV组显着降低。母羊脑尸检显示纤维化周围的不锈钢套管leptin-TV group.CONCLUSIONS：ICV应用瘦素到LV强烈减少骨形成，并导致一个非常显着的小梁骨丢失在母羊。相比之下，将瘦素ICV应用到TV中在技术上要求更高，并且结果不可预测，因为需要使用不锈钢套管诱导植入物周围纤维化，这可能阻止瘦素进入脑脊液。
BACKGROUND:Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ventricle (LV) induces bone loss in ewe. On the basis of these findings, we reasoned that the third ventricle (TV) is an even better target because of its closer location to the hypothalamus that mediates leptin effects on bone.METHODS:Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed.RESULTS:Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group.CONCLUSIONS:ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid.
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影响因子：
6.2
作者：
J. Tamasi;B. Arey;D. Bertolini;J. Feyen
通讯作者：
J. Tamasi;B. Arey;D. Bertolini;J. Feyen
DOI：
--
发表时间：
1998
期刊：
Frontiers in Bioscience
影响因子：
--
作者：
E. Thorndike;A. Turner
通讯作者：
A. Turner
影响因子：
3.3
作者：
Sigrist, Ilonka M.;Gerhardt, Christian;Egermann, Marcus
通讯作者：
Egermann, Marcus
瘦素：脂肪量对骨组织保护作用的潜在介质。
DOI：
10.1016/s1297-319x(02)00005-2
发表时间：
2003
期刊：
Joint, bone, spine : revue du rhumatisme
影响因子：
--
作者：
T. Thomas
通讯作者：
T. Thomas
影响因子：
6.2
作者：
Monier-Faugere, MC;Geng, ZP;Malluche, HH
通讯作者：
Malluche, HH