Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis
Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis
复制标题
组蛋白乙酰转移酶 GCN5 下降抑制骨质疏松症期间 BMSC 介导的血管生成
DOI：
10.1096/fj.201700118r
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发表时间：
2017-10-01
期刊：
影响因子：
4.8
通讯作者：
Jin, Yan
中科院分区：
文献类型：
--
作者：
Jing, Huan;Liao, Li;Jin, Yan
与年龄相关的骨质疏松症和绝经后骨质疏松症会破坏血管生成。然而，这种疾病的机制仍然难以捉摸。我们证实，在这项研究中，根据减少的H型血管，骨髓间充质干细胞（BMSCs）的促血管生成的潜力下降，在骨质疏松症。组蛋白乙酰转移酶家族的筛选显示，GCN 5在骨质疏松股骨来源的BMSCs中减少。进一步的分析表明，GCN 5在调节BMSC的促血管生成潜力中起重要作用。GCN 5通过增强VEGF启动子上的H3 K9 ac水平来促进BMSC介导的血管生成。骨髓间充质干细胞中GCN 5表达减少导致促血管生成能力下降。因此，GCN 5的过表达增强了增生BMSC的促血管生成能力。此外，通过慢病毒表达载体在体内恢复GCN 5表达显著减弱了卵巢切除小鼠股骨中血管生成的丧失。我们的研究结果揭示了控制BMSC介导的血管生成的表观遗传机制，并为骨质疏松症的治疗提供了新的治疗靶点。Jing，H.，廖湖，加-地苏，X.，绍伊，澳-地张，X.，邓志，Jin，Y.组蛋白乙酰转移酶GCN 5下降抑制骨质疏松症中BMSC介导的血管生成
Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs. GCN5 promoted BMSC-mediated angiogenesis by enhancing H3K9ac levels on the promoter of Vegf. The decrease of GCN5 in osteoporotic BMSCs led to the decline of proangiogenic capacity. Accordingly, overexpression of GCN5 enhanced the proangiogenic potency of osteoporotic BMSCs. Furthermore, recovering GCN5 expression in vivo by lentiviral expression vector significantly attenuated the loss of angiogenesis in ovariectomized mouse femurs. Our study results revealed an epigenetic mechanism controlling BMSC-mediated angiogenesis and provided a novel therapeutic target for osteoporosis treatment.-Jing, H., Liao, L., Su, X., Shuai, Y. Zhang, X., Deng, Z., Jin, Y. Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis.