Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice.
Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice.
复制标题
DOI：
10.3389/fphar.2022.1018480
复制
发表时间：
2022
影响因子：
5.6
通讯作者：
Cheng, Qun
中科院分区：
文献类型：
--
作者：
Zhang, Haichao;Ke, Zheng;Dong, Shuangshuang;Du, Yanping;Tang, Wenjing;Chen, Minmin;Yu, Weijia;Cheng, Qun
老年男性患者易发生骨质疏松和肌肉减少症，尤其是脆性骨折、性腺功能减退和前列腺癌患者。然而，目前，很少有治疗方法可用于患有肌肉减少症的男性。先前在卵巢切除大鼠中的临床前研究显示了艾地骨化醇在改善骨强度和肌肉萎缩方面的有希望的作用。因此，我们研究了艾地骨化醇对雄激素缺乏雄性小鼠的影响。6周龄的雄性小鼠接受睾丸切除术（ORX）或假手术。将小鼠随机分为4组（n = 12/组），包括1）假手术小鼠，2）ORX组，3）ORX艾地骨化醇30 ng/kg，和4）ORX艾地骨化醇50 ng/kg。依地骨化醇增加ORX小鼠的骨量和股骨强度。艾地骨化醇30 ng/kg剂量完全挽救了ORX诱导的肌无力。RT-qPCR结果显示，艾地骨化醇可提高I型和IIa型纤维的mRNA水平。艾地骨化醇组腓肠肌MuRF 1和Atrogin-1的表达水平明显低于ORX组。据推测，艾地骨化醇可能通过PI 3 K/AKT/FOXO信号通路发挥作用。这些发现为评价艾地骨化醇作为男性肌肉减少症和骨质疏松症患者的研究性治疗提供了证据。
Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.
登录
查看更多内容
影响因子：
1.2
作者：
Hayakawa, Naohiko;Fukumura, Junko;Kitamura, Hidemitsu
通讯作者：
Kitamura, Hidemitsu
影响因子：
3.2
作者：
Aloia, John F.;Katumuluwa, Subhashini;Islam, Shahidul
通讯作者：
Islam, Shahidul
影响因子：
--
作者：
Davis, Jennifer S.;Nastiuk, Kent L.;Krolewski, John J.
通讯作者：
Krolewski, John J.
影响因子：
4.1
作者：
Besschetnova, Tatiana;Brooks, Daniel J.;Lanske, Beate
通讯作者：
Lanske, Beate
影响因子：
3.3
作者：
Cetrone, Michela;Mele, Antonietta;Tricarico, Domenico
通讯作者：
Tricarico, Domenico