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MicroRNA-672-5p Identified during Weaning Reverses Osteopenia and Sarcopenia in Ovariectomized Mice
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2019-01-10 , DOI: 10.1016/j.omtn.2019.01.002
Naseer Ahmad 1 , Priyanka Kushwaha 1 , Anirudha Karvande 1 , Ashish Kumar Tripathi 1 , Priyanka Kothari 1 , Sulekha Adhikary 1 , Vikram Khedgikar 1 , Vijay Kumar Mishra 1 , Ritu Trivedi 1
Affiliation  

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.



中文翻译:


断奶期间鉴定出的 MicroRNA-672-5p 可逆转卵巢切除小鼠的骨质减少和肌肉减少症



绝经后状况会加剧生物衰老过程,其特征是多种代谢紊乱,其中骨质流失是最普遍的结果,并且通常伴有肌肉减少症。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带来更糟糕的健康结果。产前和产后的骨骼发育需要在怀孕和哺乳期间从母体向胎儿提供钙,从而导致母体骨骼明显损失。它遵循断奶前后的合成代谢阶段,在此期间母体骨骼显着恢复。在这里,我们研究了在断奶期间主要表达的 microRNA-672-5p 在卵巢切除小鼠中对骨质减少和肌肉减少症的治疗效果。 miR-672-5p 诱导成骨细胞分化和矿化。这些作用是通过抑制 Smurf1 并增强 Runx2 转录激活来介导的。在体内,miR-672-5p显着增加成骨细胞生成和矿化,从而逆转卵巢切除术引起的骨质流失。它还提高了骨矿物质密度、承载能力和骨质量。 miR-672-5p 也减轻了肌肉减少症,因为我们观察到肌纤维的横截面积和费雷特直径增加。我们假设 miR-672-5p 表达升高对雌激素缺乏引起的骨质减少和肌肉减少症具有治疗功效。

更新日期:2019-01-10
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