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MicroRNA-365 functions as a mechanosensitive microRNA to inhibit end plate chondrocyte degeneration by targeting histone deacetylase 4

文献类型：期刊论文

作者Zheng, Quan1,2; Li, Xing-xing1; Shao, Song1; Jiang, Huai1; Sun, Liang-ye1; Xiao, Liang2; Xu, Hong-guang2; Zhang, Xiao-ling3,4,5; ,
刊名BONE
出版日期2019
卷号128期号:-页码:115052
关键词Mechanical tension End plate chondrocyte Degeneration MiR-365 HDAC4 Wnt/beta-catenin
ISSN号8756-3282
DOI10.1016/j.bone.2019.115052
文献子类Article
英文摘要End plate chondrocyte degeneration is a major cause of intervertebral disc degeneration. Mechanical biophysical forces, including intermittent cyclic mechanical tension (ICMT), exacerbate end plate chondrocyte degeneration. However, the underlying molecular mechanism of mechanical stretch-induced end plate chondrocyte degeneration is still unclear. This study sought to determine whether microRNAs (miRNAs) respond to mechanical stretch and play a role in regulating mechanically-induced end plate chondrocyte degeneration. We identified miR-365 as a mechanoresponsive miRNA in primary human end plate chondrocytes after ICMT application by miRNA microarray analysis. The expression of miR-365 was down-regulated in the disc samples obtained from patients with disc degeneration. We also found that the miR-365 stimulates chondrocyte proliferation but does not promote end plate chondrocyte death. Using bioinformatic analyses and subsequent confirmation by real-time RT-PCR, we identified multiple candidate target genes of miR-365 that responded to in vitro mechanical stimulation; among them, HDAC4 was fully characterized. Mutation of putative miR-365 binding sites in HDAC4 mRNA abolished miR-365 mediated repression of HDAC4 3'-untranslated region (3'UTR) luciferase reporter activity, suggesting that miR-365 binds to the HDAC4 3'UTR. Overexpression of miR-365 significantly decreased the HDAC4 protein level, suggesting that miR-365 acts as an endogenous attenuator of HDAC4 in human end plate chondrocytes. Further, perturbation of miR-365 expression also had a significant effect on the expression of COL2A and ACAN and on matrix degeneration. Overexpression of HDAC4 abolished miR-365 rescued end plate chondrocyte degeneration during ICMT application. Furthermore, we found that the wnt/beta-catenin signal pathway was related to HDAC4 and promoted end plate chondrocyte degeneration. Overall, our results suggest that miR-365 is a mechanosensitive miRNA that regulates human chondrocyte degeneration by directly targeting HDAC4. We propose that therapeutic regulation of miR-365 may be an efficient anabolic strategy for inhibiting end plate chondrocyte degeneration.
学科主题Food Science & Technology ; Toxicology
WOS关键词DISC DEGENERATION ; GENE-EXPRESSION ; OSTEOARTHRITIS ; DIFFERENTIATION ; APOPTOSIS ; LOAD
语种英语
CSCD记录号CSCD:31472300
WOS记录号WOS:000493584700016
出版者ELSEVIER SCIENCE INC
版本出版稿
源URL[http://202.127.25.144/handle/331004/1202]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Anhui Med Univ, Luan Hosp, Luan Peoples Hosp, Dept Orthoped Surg, Luan 237001, Anhui, Peoples R China;
2.Wannan Med Coll, Affiliated Hosp 1, Key Lab Noncoding RNA Transformat Res Anhui Highe, Spine Res Ctr,Dept Spine Surg,Yijishan Hosp, Wuhu 241001, Anhui, Peoples R China;
3.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Orthoped Surg, Shanghai 200011, Peoples R China;
4.Shanghai Jiao Tong Univ, Chinese Acad Sci, Sch Med, Key Lab Stem Cell Biol,Inst Hlth Sci, Shanghai 200031, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China,
推荐引用方式
GB/T 7714		 Zheng, Quan,Li, Xing-xing,Shao, Song,et al. MicroRNA-365 functions as a mechanosensitive microRNA to inhibit end plate chondrocyte degeneration by targeting histone deacetylase 4[J]. BONE,2019,128(-):115052.
APA Zheng, Quan.,Li, Xing-xing.,Shao, Song.,Jiang, Huai.,Sun, Liang-ye.,...&,.(2019).MicroRNA-365 functions as a mechanosensitive microRNA to inhibit end plate chondrocyte degeneration by targeting histone deacetylase 4.BONE,128(-),115052.
MLA Zheng, Quan,et al."MicroRNA-365 functions as a mechanosensitive microRNA to inhibit end plate chondrocyte degeneration by targeting histone deacetylase 4".BONE 128.-(2019):115052.

入库方式： OAI收割

来源：上海营养与健康研究所

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