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Urine-derived stem cells-extracellular vesicles ameliorate diabetic osteoporosis through HDAC4/HIF-1α/VEGFA axis by delivering microRNA-26a-5p
Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2022-05-13 , DOI: 10.1007/s10565-022-09713-5
Dan Zhang 1 , Jian Du 1 , Min Yu 2 , Linna Suo 1
Affiliation  

Critical roles of stem cell-extracellular vesicles (EVs) in the management of osteoporosis have been documented. Here, this study was designed to enlarge the research of the specific effects and underlying mechanism of urine-derived stem cells-EVs (USCs-EVs) on osteoporosis in diabetes rats. Firstly, miR-26a-5p and histone deacetylase 4 (HDAC4) expression in USCs of rats after diabetic osteoporosis (DOP) modeling induced by streptozotocin injection was determined, followed by study of their interaction. Then, USCs-EVs were co-cultured with osteogenic precursor cells, the effects of miRNA-26a-5p (miR-26a-5p) on osteoblasts, osteoclasts, bone mineralization deposition rate were evaluated. Meanwhile, the effect of USCs-EVs carrying miR-26a-5p on DOP rats was assessed. Elevated miR-26a-5p was seen in USCs-EVs which limited HDAC4 expression. Moreover, USCs-EVs delivered miR-26a-5p to osteogenic precursor cells, thereby promoting their differentiation, enhancing the activity of osteoblasts, and inhibiting the activity of osteoclasts, thereby preventing DOP through the activation of hypoxia inducible factor 1 subunit alpha (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway by repressing HDAC4. In a word, USCs-EVs-miR-26a-5p is a promising therapy for DOP by activating HIF-1α/VEGFA pathway through HDAC4 inhibition.

Graphical abstract

1. USCs-EVs-miR-26a-5p targeted HDAC4 and limited HDAC4 expression. 2. miR-26a-5p was delivered by USCs-EVs into osteoblast precursor cells. 3. USCs-EVs-miR-26a-5p promoted the differentiation of osteoblast precursor cells into osteoblasts. 4. miR-26a-5p delivered by USCs-EVs could inhibit HDAC4. 5. USCs-EVs-miR-26a-5p could prevent the pathogenesis of DOP via HIF-1α/VEGFA aix.



中文翻译:

尿源干细胞-细胞外囊泡通过 HDAC4/HIF-1α/VEGFA 轴传递 microRNA-26a-5p 改善糖尿病骨质疏松症

干细胞-细胞外囊泡(EV)在骨质疏松症治疗中的关键作用已被记录。本研究旨在扩大尿源性干细胞-EVs(USCs-EVs)对糖尿病大鼠骨质疏松症的具体作用和潜在机制的研究。首先测定注射链脲佐菌素诱导糖尿病骨质疏松(DOP)模型后大鼠USCs中miR-26a-5p和组蛋白脱乙酰酶4(HDAC4)的表达,并研究它们之间的相互作用。然后,将USCs-EVs与成骨前体细胞共培养,评估miRNA-26a-5p(miR-26a-5p)对成骨细胞、破骨细胞、骨矿化沉积率的影响。同时,评估了携带miR-26a-5p的USCs-EVs对DOP大鼠的影响。在 USC-EV 中观察到 miR-26a-5p 升高,这限制了 HDAC4 的表达。此外,USCs-EVs将miR-26a-5p递送至成骨前体细胞,从而促进其分化,增强成骨细胞的活性,并抑制破骨细胞的活性,从而通过激活缺氧诱导因子1亚基α(HIF- 1α)/血管内皮生长因子 A (VEGFA) 通路通过抑制 HDAC4 来实现。总之,USCs-EVs-miR-26a-5p 通过抑制 HDAC4 激活 HIF-1α/VEGFA 通路,是一种有前景的 DOP 治疗方法。

图形概要

1. USCs-EVs-miR-26a-5p 靶向 HDAC4 并限制 HDAC4 表达。2. miR-26a-5p由USCs-EVs递送至成骨细胞前体细胞中。3. USCs-EVs-miR-26a-5p促进成骨前体细胞向成骨细胞分化。4. USCs-EVs 传递的 miR-26a-5p 可以抑制 HDAC4。5. USCs-EVs-miR-26a-5p可以通过HIF-1α/VEGFA aix预防DOP的发病。

更新日期:2022-05-13
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