Treadmill training regulates β-catenin signaling through phosphorylation of GSK-3β in lumbar vertebrae of ovariectomized rats
Treadmill training regulates β-catenin signaling through phosphorylation of GSK-3β in lumbar vertebrae of ovariectomized rats
复制标题
DOI：
10.1007/s00421-011-2306-4
复制
发表时间：
2012-09-01
影响因子：
3
通讯作者：
Ji, Gang
中科院分区：
文献类型：
--
作者：
Bu, Shumin;Chen, Yu;Ji, Gang
绝经后骨质疏松症与骨髓中高水平的脂肪生成有关，而成骨细胞的数量减少。通过糖原合成酶激酶-3 β（GSK-3 β）的磷酸化对β-连环蛋白的机械作用对于体外抑制间充质干细胞中的脂肪生成是至关重要的。在本研究中，我们假设跑台训练可以通过磷酸化GSK-3 β来调节去卵巢大鼠腰椎中的β-catenin信号。将3月龄雌性Sprague-Dawley大鼠随机分为以下4组：（a）假手术组，（B）去卵巢组，（c）去卵巢运动组（EX）和（d）去卵巢雌激素替代组（E-2）。在实验结束时，分析血清雌二醇（E-2）和黄体生成素（LH）水平，最终腰椎强度，以及腰椎中过氧化物酶体增殖物激活受体γ（PPAR γ）、β-连环蛋白、P-GSK-3 β和osterix（Osx）的蛋白表达。此外，还检测了子宫中β-连环蛋白和P-GSK-3 β的蛋白表达。与久坐OVX组相比，EX组的PPAR γ蛋白水平较低，腰椎极限强度较高，腰椎体中β-连环蛋白和P-GSK-3 β蛋白水平较高。EX治疗对骨中β-连环蛋白和P-GSK-3 β蛋白水平的影响在子宫中不可重现。此外，运动治疗没有产生雌激素样作用，证明了血清LH水平。本研究提示，跑台训练可激活OVX大鼠腰椎GSK-3 beta/beta-catenin信号通路，抑制PPAR γ的产生，这可能有助于预防OVX大鼠的骨丢失。
Postmenopausal osteoporosis is associated with high level of adipogenesis within the bone marrow at the expense of osteoblast population. The mechanical effect on beta-catenin through phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta) is critical for inhibition of adipogenesis in mesenchymal stem cells in vitro. In present study, we hypothesized that treadmill training could regulate the beta-catenin signaling through phosphorylation of GSK-3 beta in the lumbar vertebrae of ovariectomized (OVX) rats. 3-month-old female Sprague-Dawley rats were divided randomly into the following four groups: (a) Sham, (b) OVX, (c) OVX exercised (EX), and (d) OVX estrogen replacement (E-2). At the end of the experiment, the serum levels of estradiol (E-2) and luteinizing hormone (LH), the ultimate lumbar vertebra strength, as well as the protein expression for peroxisome proliferators-activated receptor gamma (PPAR gamma), beta-catenin, P-GSK-3 beta, and osterix (Osx) in lumbar vertebrae were analyzed. Moreover, the protein expression for beta-catenin and P-GSK-3 beta were also examined in the uterus. The EX group had lower protein level of PPAR gamma, higher ultimate lumbar vertebral strength, and higher protein levels of beta-catenin, and P-GSK-3 beta in lumbar vertebral bodies compared with sedentary OVX group. The effects of EX treatment on the protein levels of beta-catenin and P-GSK-3 beta in bones were not reproducible in the uterus. Moreover, exercise treatment produced no estrogenic effect as evidenced by serum level of LH. In conclusion, this study suggested that treadmill training could activate the GSK-3 beta/beta-catenin signaling and inhibit the production of PPAR gamma in lumbar vertebrae of OVX rats, which may contribute to the prevention of bone loss in OVX rats.