Chronic Alcohol Reduces Bone Mass Through Inhibiting Proliferation and Promoting Aging of Endothelial Cells in Type-H Vessels
Chronic Alcohol Reduces Bone Mass Through Inhibiting Proliferation and Promoting Aging of Endothelial Cells in Type-H Vessels
复制标题
长期饮酒通过抑制H型血管内皮细胞增殖和促进衰老来减少骨量
DOI：
10.1089/scd.2021.0337
复制
发表时间：
2022-08-22
影响因子：
4
通讯作者：
Jin, Jianliang
中科院分区：
文献类型：
--
作者：
Chen, Ao;Li, Xiaoting;Jin, Jianliang
饮酒被认为是继发性骨质减少的主要危险因素之一。由H型血管偶联的血管生成和骨生成协调骨稳态的生物学过程以防止骨质减少。本研究旨在确定慢性酒精是否抑制H型血管依赖性骨形成。2月龄小鼠每天用5%（v/v）酒精流质饮食（28%的热量）或正常流质饮食喂养2个月。分离胫骨，用X线和微型计算机断层扫描进行检测。制备石蜡包埋或冷冻胫骨切片，分别用于免疫组织化学或免疫荧光染色。将人脐静脉内皮细胞（HUVEC）用不同浓度的酒精处理12小时，所述酒精包括0 mM（0%）、8.7 mM（0.5%）、52 mM（3%）或87 mM（5%）酒精。收集上述HUVEC细胞的条件培养基培养人骨髓间充质干细胞（BM-MSCs），体外诱导其向成骨细胞分化。酒精性饮食可通过抑制内皮细胞增殖和促进内皮细胞老化，抑制小鼠骨生长，导致骨质疏松，损害成骨细胞的骨形成，减少CD 31（hi）EMCN（hi）H型血管形成。与对照组相比，酒精处理组p16蛋白表达明显增加，Bmi-1、CDK 6、Cyclin D、E2 F1和BMP-2蛋白表达明显减少。乙醇通过减少H型血管内皮细胞分泌BMP 2抑制BM-MSCs向成骨细胞分化。酒精饮食通过Bmi-1/p16信号通路抑制内皮细胞增殖和促进衰老，从而抑制CD 31（hi）EMCN（hi）H型血管形成;通过减少H型血管内皮细胞分泌BMP 2，抑制BM-MSCs向成骨细胞分化。本研究为开发一种新的治疗策略提供了基础，该策略靶向衰老的H型血管内皮细胞，以防止酒精性骨质减少。
Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. This study aimed to determine whether chronic alcohol inhibits type-H vessel-dependent bone formation. Two-month-old mice were fed with 5% (v/v) alcohol liquid diet (28% of calories) or normal liquid diet every day for 2 months. The tibias were isolated and detected with X-ray and microcomputed tomography. Paraffin-embedded or frozen tibial sections were prepared and used for immunohistochemical or immunofluorescence staining, respectively. Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of alcohol, including 0 mM (0%), 8.7 mM (0.5%), 52 mM (3%), or 87 mM (5%) alcohol for 12 h. The conditioned medium of the above HUVEC cells was collected to culture human bone marrow-mesenchymal stem cells (BM-MSCs), which were induced to differentiate into osteoblasts in vitro. The alcoholic diet retarded the bone growth and led to osteoporosis, impaired bone formation of osteoblasts, and decreased CD31(hi)EMCN(hi) type-H vessel formation through inhibiting proliferation and promoting aging of endothelial cells in mice. Alcohol treatment obviously increased the expression of p16, while significantly decreased the expression of Bmi-1, CDK6, Cyclin D, E2F1, and bone morphogenetic protein (BMP)2 compared with vehicle. Alcohol inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. Alcoholic diet impaired CD31(hi)EMCN(hi) type-H vessel formation through inhibiting proliferation and promoting aging of endothelial cells through Bmi-1/p16 signaling, and inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. This study provides a basis for developing a new treatment strategy targeting aging endothelial cells of type-H vessel to prevent alcoholic osteopenia.