miR-29a promotes osteoblast proliferation by downregulating DKK-1 expression and activating Wnt/β-catenin signaling pathway

被引:26
作者
Zhang, Fuwen [1 ]
Cao, Kun [1 ]
Du, Gongwen [1 ]
Zhang, Qi [1 ]
Yin, Zongsheng [1 ]
机构
[1] Anhui Med Univ, Hosp 1, Hefei, Anhui, Peoples R China
来源
ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE | 2019年 / 28卷 / 10期
关键词
beta-catenin; Dkk-1; miR-29a; si-RNA; MESENCHYMAL STEM-CELLS; DIFFERENTIATION; SUPPRESSION;
D O I
10.17219/acem/104533
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background. MicroRNA (miRNA) is a kind of non-coding small RNA with a negative regulating function. Some miRNAs play a role in regulating the differentiation and function of osteoblasts, chondrocytes and osteoclasts. Objectives. In this study, we analyzed the role of miR-29a and dickkopf-1 (DKK-1) in osteoblast differentiation. Material and methods. Specimens were collected from the surgical resection of pathological a n kylosing spondylitis (AS) tissue and some normal tissues. The expression of miR-29a, DKK-1 and beta-catenin in normal and AS tissues were detected with real-time polymerase chain reaction (RT-PCR) and western blotting. Cell proliferation was detected with a Cell Counting Kit-8, cell migration and invasion were determined using a Transwell system and cell apoptosis was analyzed with flow cytometry. The luciferase reporter gene plasmid pGL3-DKK-1 and a point-mutation of the luciferase reporter gene plasmid mut-pGL3-DKK-1 were constructed. Results. It was found that miR-29a could promote the proliferation of hFOB1.19 cells, while DKK-1 inhibited their proliferation. Also, miR-29a was able to inhibit the apoptosis of hFOB1.19 cells, while DKK-1 was able to promote the apoptosis of hFOB1.19 cells. When it comes to the invasion and migration of hFOB1.19 cells, miR-29a was found to promote it, while DKK-1 did not. Conclusions. These findings will lead to a better understanding of the proliferation and differentiation of osteoblasts and will provide new insights for the treatment of this disease.
引用
收藏
页码:1293 / 1300
页数:8
相关论文
共 23 条
[1]   A critical role for endocytosis in Wnt signaling [J].
Blitzer, Jeremy T. ;
Nusse, Roel .
BMC CELL BIOLOGY, 2006, 7 (1)
[2]   MicroRNA-34a Inhibits Osteoblast Differentiation and In Vivo Bone Formation of Human Stromal Stem Cells [J].
Chen, Li ;
Holmstrom, Kim ;
Qiu, Weimin ;
Ditzel, Nicholas ;
Shi, Kaikai ;
Hokland, Lea ;
Kassem, Moustapha .
STEM CELLS, 2014, 32 (04) :902-912
[3]   Wnt/β-Catenin Signaling and Disease [J].
Clevers, Hans ;
Nusse, Roel .
CELL, 2012, 149 (06) :1192-1205
[4]  
Cuenca PD, 2017, J MED FOOD, V20, P653
[5]   Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes [J].
Hill, TP ;
Später, D ;
Taketo, MM ;
Birchmeier, W ;
Hartmann, C .
DEVELOPMENTAL CELL, 2005, 8 (05) :727-738
[6]   Signaling and transcriptional regulation in osteoblast commitment and differentiation [J].
Huang, Wei ;
Yang, Shuying ;
Shao, Jianzhong ;
Li, Yi-Ping .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2007, 12 :3068-3092
[7]   Identification of novel microRNA inhibiting actin cytoskeletal rearrangement thereby suppressing osteoblast differentiation [J].
John, Aijaz A. ;
Prakash, Ravi ;
Kureel, Jyoti ;
Singh, Divya .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2018, 96 (05) :427-444
[8]   miR-29 Modulates Wnt Signaling in Human Osteoblasts through a Positive Feedback Loop [J].
Kapinas, Kristina ;
Kessler, Catherine ;
Ricks, Tinisha ;
Gronowicz, Gloria ;
Delany, Anne M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (33) :25221-25231
[9]   miR-29 Suppression of Osteonectin in Osteoblasts: Regulation During Differentiation and by Canonical Wnt Signaling [J].
Kapinas, Kristina ;
Kessler, Catherine B. ;
Delany, Anne M. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2009, 108 (01) :216-224
[10]   MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast differentiation by regulating β-catenin acetylation [J].
Ko, Jih-Yang ;
Chuang, Pei-Chin ;
Chen, Ming-Wen ;
Ke, Huei-Ching ;
Wu, Shin-Long ;
Chang, Yu-Hsuan ;
Chen, Yu-Shan ;
Wang, Feng-Sheng .
BONE, 2013, 57 (02) :468-475