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Maternal high protein-diet programs impairment of offspring's bone mass through miR-24-1-5p mediated targeting of SMAD5 in osteoblasts.
Cellular and Molecular Life Sciences ( IF 6.2 ) Pub Date : 2020-07-30 , DOI: 10.1007/s00018-020-03608-6
Govindraj Ellur 1, 2 , Shinde Vijay Sukhdeo 3 , Md Touseef Khan 1, 2 , Kunal Sharan 1, 2
Affiliation  

Maternal nutrition is crucial for the offspring's skeleton development and the onset of osteoporosis later in life. While maternal low protein diet has been shown to regulate bone mass negatively, the effect of a high protein diet (HP) remains unexplored. Here, we found that C57BL/6 mice fed with HP delivered offspring with decreased skeletal mineralization at birth and reduced bone mass throughout their life due to a decline in their osteoblast maturation. A small RNA sequencing study revealed that miR-24-1-5p was highly upregulated in HP group osteoblasts. Target prediction and validation studies identified SMAD-5 as a direct target of miR-24-1-5p. Furthermore, mimic and inhibitor studies showed a negative correlation between miR-24-1-5p expression and osteoblast function. Moreover, ex vivo inhibition of miR-24-1-5p reversed the reduced maturation and SMAD-5 expression in the HP group osteoblasts. Together, we show that maternal HP diminishes the bone mass of the offspring through miR-24-1-5p.

中文翻译:


母亲的高蛋白饮食通过 miR-24-1-5p 介导的成骨细胞中 SMAD5 的靶向作用来损害后代的骨量。



母体营养对于后代的骨骼发育和晚年骨质疏松症的发病至关重要。虽然母亲低蛋白饮食已被证明会对骨量产生负面影响,但高蛋白饮食 (HP) 的影响仍有待探索。在这里,我们发现用 HP 喂养的 C57BL/6 小鼠生下的后代在出生时骨骼矿化降低,并且由于成骨细胞成熟度下降而导致其一生中骨量减少。一项小 RNA 测序研究表明,miR-24-1-5p 在 HP 组成骨细胞中高度上调。靶标预测和验证研究确定 SMAD-5 是 miR-24-1-5p 的直接靶标。此外,模拟物和抑制剂研究显示 miR-24-1-5p 表达与成骨细胞功能之间呈负相关。此外,体外抑制 miR-24-1-5p 可逆转 HP 组成骨细胞成熟度和​​ SMAD-5 表达的降低。总之,我们发现母体 HP 通过 miR-24-1-5p 减少后代的骨量。
更新日期:2020-07-30
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