lncRNA Rmst acts as an important mediator of BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by antagonizing Notch-targeting microRNAs

被引：25

作者：

Zhang, Zhicai ^{[1
,2
]}

Liu, Jianxiang ^{[1
,2
]}

Zeng, Zongyue ^{[2
,3
,4
,5
]}

Fan, Jiaming ^{[2
,3
,4
,5
]}

Huang, Shifeng ^{[2
,3
,4
,5
]}

Zhang, Linghuan ^{[2
,3
,4
,5
]}

Zhang, Bo ^{[2
,6
,7
,8
,9
,10
,11
]}

Wang, Xi ^{[2
,3
,4
,5
]}

Feng, Yixiao ^{[2
,3
,4
,5
]}

Ye, Zhenyu ^{[2
,12
]}

Zhao, Ling ^{[2
,3
,4
,5
]}

Cao, Daigui ^{[2
,3
,4
,5
,13
,14
]}

Yang, Lijuan ^{[2
,6
,7
,8
,9
,10
,11
]}

Pakvasa, Mikhail ^{[2
]}

Liu, Bin ^{[2
,15
]}

Wagstaff, William ^{[2
]}

Wu, Xiaoxing ^{[2
,3
,4
,5
]}

Luo, Huaxiu ^{[2
,16
]}

Zhang, Jing ^{[2
,3
,4
,5
]}

Zhang, Meng ^{[2
,17
]}

He, Fang ^{[2
,3
,4
,5
]}

Mao, Yukun ^{[2
,18
]}

Ding, Huimin ^{[2
,19
]}

Zhang, Yongtao ^{[2
,20
]}

Niu, Changchun ^{[2
,13
,14
]}

Haydon, Rex C. ^{[2
]}

Luu, Hue H. ^{[2
]}

Lee, Michael J. ^{[2
]}

Wolf, Jennifer Moriatis ^{[2
]}

Shao, Zengwu ^{[1
]}

He, Tong-Chuan ^{[2
]}

机构：

[1] Huazhong Univ Sci & Technol, Union Hosp, Dept Orthopaed, Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China

[2] Univ Chicago, Med Ctr, Mol Oncol Lab, Dept Orthopaed Surg & Rehabil Med, Chicago, IL 60637 USA

[3] Chongqing Med Univ, Minist Educ, Key Lab Diagnost Med, Chongqing 400016, Peoples R China

[4] Chongqing Med Univ, Sch Lab Med, Chongqing 400016, Peoples R China

[5] Chongqing Med Univ, Affiliated Hosp, Chongqing 400016, Peoples R China

[6] Lanzhou Univ, Key Lab Orthopaed Surg Gansu Prov, Hosp 1, Lanzhou 730030, Gansu, Peoples R China

[7] Lanzhou Univ, Dept Orthopaed Surg, Hosp 1, Lanzhou 730030, Gansu, Peoples R China

[8] Lanzhou Univ, Dept Obstet & Gynecol, Hosp 1, Lanzhou 730030, Gansu, Peoples R China

[9] Lanzhou Univ, Key Lab Orthopaed Surg Gansu Prov, Hosp 2, Lanzhou 730030, Gansu, Peoples R China

[10] Lanzhou Univ, Dept Orthopaed Surg, Hosp 2, Lanzhou 730030, Gansu, Peoples R China

[11] Lanzhou Univ, Dept Obstet & Gynecol, Hosp 2, Lanzhou 730030, Gansu, Peoples R China

[12] Soochow Univ, Dept Gen Surg, Affiliated Hosp 2, Suzhou 215004, Peoples R China

[13] Chongqing Gen Hosp, Dept Orthopaed Surg, Chongqing 400013, Peoples R China

[14] Chongqing Gen Hosp, Dept Lab Med, Chongqing 400013, Peoples R China

[15] Southwest Univ, Sch Life Sci, Chongqing 400715, Peoples R China

[16] Sichuan Univ, Dept Burn & Plast Surg, West China Hosp, Chengdu 610041, Sichuan, Peoples R China

[17] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Orthopaed Surg, Guangzhou 510405, Guangdong, Peoples R China

[18] Wuhan Univ, Dept Orthopaed Surg, Affiliated Zhongnan Hosp, Wuhan 430072, Hubei, Peoples R China

[19] Nanjing Med Univ, Dept Orthopaed Surg, BenQ Med Ctr, Nanjing 210000, Jiangsu, Peoples R China

[20] Qingdao Univ, Dept Orthopaed Surg, Affiliated Hosp, Qingdao 266061, Shandong, Peoples R China

来源：

AGING-US | 2019年 / 11卷 / 24期

基金：

美国国家卫生研究院;

关键词：

mesenchymal stem cells; BMP9; long noncoding RNAs; IncRNA Rmst; miRNAs; LONG NONCODING RNA; BONE MORPHOGENETIC PROTEINS; HUMAN OSTEOSARCOMA GROWTH; OSTEOBLAST DIFFERENTIATION; OSTEO/ODONTOBLASTIC DIFFERENTIATION; PERVASIVE TRANSCRIPTION; 9; BMP9; WNT; GENE; PROLIFERATION;

D O I：

10.18632/aging.102583

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Understanding the bone and musculoskeletal system is essential to maintain the health and quality of life of our aging society. Mesenchymal stem cells (MSCs) can undergo self-renewal and differentiate into multiple tissue types including bone. We demonstrated that BMP9 is the most potent osteogenic factors although molecular mechanism underlying BMP9 action is not fully understood. Long noncoding RNAs (lncRNAs) play important regulatory roles in many physiological and/or pathologic processes. Here, we investigated the role of lncRNA Rmst in BMP9-induced osteogenic differentiation of MSCs. We found that Rmst was induced by BMP9 through Smad signaling in MSCs. Rmst knockdown diminished BMP9-induced osteogenic, chondrogenic and adipogenic differentiation in vitro, and attenuated BMP9-induced ectopic bone formation. Silencing Rmst decreased the expression of Notch receptors and ligands. Bioinformatic analysis predicted Rmst could directly bind to eight Notch-targeting miRNAs, six of which were downregulated by BMP9. Silencing Rmst restored the expression of four microRNAs (miRNAs). Furthermore, an activating Notch mutant NICD1 effectively rescued the decreased ALP activity caused by Rmst silencing. Collectively, our results strongly suggest that the Rmst-miRNA-Notch regulatory axis may play an important role in mediating BMP9-induced osteogenic differentiation of MSCs.

引用

页码：12476 / 12496

页数：21

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