MicroRNA-672-5p Identified during Weaning Reverses Osteopenia and Sarcopenia in Ovariectomized Mice
MicroRNA-672-5p Identified during Weaning Reverses Osteopenia and Sarcopenia in Ovariectomized Mice
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DOI：
10.1016/j.omtn.2019.01.002
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发表时间：
2019-03-01
影响因子：
8.8
通讯作者：
Trivedi, Ritu
中科院分区：
文献类型：
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作者：
Ahmad, Naseer;Kushwaha, Priyanka;Trivedi, Ritu
绝经后的情况加剧了生物衰老过程，以多种代谢紊乱为特征，其中骨丢失是最常见的结果，通常伴随着骨质疏松症。与仅患有骨质疏松症的个体相比，这种相关发病机制的共存会导致更糟糕的健康结果。在怀孕和哺乳期间，出生前和出生后的骨骼发育需要从母亲到胎儿的钙，导致母亲严重的骨骼损失。它遵循着断奶前后的合成代谢阶段，在此期间，母体骨骼有明显的恢复。在这里，我们研究了在断奶期间确定的microRNA-672-5p在卵巢切除小鼠中主要表达时对骨量减少和骨量减少的治疗效果。MIR-672-5P诱导成骨细胞分化和矿化。这些作用是通过抑制SMurf1和增强Runx2转录激活来实现的。在体内，miR-672-5P显著增加成骨细胞的生成和矿化，从而逆转卵巢切除所致的骨丢失。它还改善了骨矿密度、承载能力和骨骼质量。MiR-672-5P还可减轻肌纤维减少症，因为我们观察到肌纤维横截面积和费雷特直径增加。我们推测，miR-672-5p的高表达对雌激素缺乏所致的骨量减少和骨质疏松症有疗效。
Post-menopausal condition augments the biological aging process, characterized by multiple metabolic disorders in which bone loss is the most prevalent outcome and usually coupled with sarcopenia. Coexistence of such associated pathogenesis have much worse health outcomes, compared to individuals with osteoporosis only. Pre- and post-natal bone development demands calcium from mother to fetus during pregnancy and lactation leading to a significant maternal skeletal loss. It follows an anabolic phase around weaning during which there is a notable recovery of the maternal skeleton. Here, we have studied the therapeutic effect of microRNA-672-5p identified during weaning when it is predominantly expressed, in ovariectomized mice for both osteopenia and sarcopenia. miR-672-5p induced osteoblast differentiation and mineralization. These actions were mediated through inhibition of Smurf1 with enhanced Runx2 transcriptional activation. In vivo, miR-672-5p significantly increased osteoblastogenesis and mineralization, thus reversing bone loss caused by ovariectomy. It also improved bone-mineral density, load-bearing capacity, and bone quality. Sarcopenia was also alleviated by miR-672-5p, as we observed increased cross-sectional area and Feret's diameter of muscle fibers. We hypothesize that elevated miR-672-5p expression has therapeutic efficacy in estrogen-deficiency-induced osteopenia along with sarcopenia.