Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression

被引：16

作者：

Zhe Ruan ^{[1
,2
]}

Hao Yin ^{[1
,2
,3
,4
]}

TengFei Wan ^{[1
,2
,3
,4
]}

ZhiRou Lin ^{[5
]}

ShuShan Zhao ^{[1
]}

HaiTao Long ^{[1
]}

Cheng Long ^{[1
]}

ZhaoHui Li ^{[1
]}

YuQi Liu ^{[1
]}

Hao Luo ^{[1
]}

Liang Cheng ^{[1
]}

Can Chen ^{[1
]}

Min Zeng ^{[1
]}

ZhangYuan Lin ^{[1
]}

RuiBo Zhao ^{[1
]}

ChunYuan Chen ^{[1
,2
,3
,4
,6
]}

ZhenXing Wang ^{[1
,2
,3
,4
,6
]}

ZhengZhao Liu ^{[1
,2
,3
,4
,6
]}

Jia Cao ^{[1
,2
,3
,4
,6
]}

YiYi Wang ^{[1
,2
,3
,4
]}

Ling Jin ^{[1
,2
,3
,4
]}

YiWei Liu ^{[1
,2
,3
,4
]}

GuoQiang Zhu ^{[1
,2
,3
,4
]}

JingTao Zou ^{[1
,2
,3
,4
]}

JiangShan Gong ^{[1
,2
,3
,4
]}

Yi Luo ^{[1
,2
,3
,4
]}

Yin Hu ^{[5
]}

Yong Zhu ^{[1
]}

Hui Xie ^{[1
,2
,3
,4
,6
]}

机构：

[1] Department of Orthopedics, Xiangya Hospital, Central South University

[2] Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University

[3] Hunan Key Laboratory of Angmedicine

[4] Angmedicine Research Center of Central South University

[5] The First Affiliated Hospital, Department of Metabolism and Endocrinology, Hengyang Medical School, University of South China

[6] National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University

来源：

Bone Research | 2023年 / 03期

关键词：

D O I：

暂无

中图分类号：

R683 [骨折、骨的损伤];

学科分类号：

100220 [骨科学];

摘要：

<正>Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.

引用

页码：625 / 637

页数：13

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