PMID- 36308623 OWN - NLM STAT- MEDLINE DCOM- 20230227 LR - 20230308 IS - 1573-675X (Electronic) IS - 1360-8185 (Linking) VI - 28 IP - 1-2 DP - 2023 Feb TI - Exploration of microRNA-106b-5p as a therapeutic target in intervertebral disc degeneration: a preclinical study. PG - 199-209 LID - 10.1007/s10495-022-01773-6 [doi] AB - MicroRNA (miRNA) has emerge as a vital regulator in the pathogenesis of intervertebral disc degeneration (IDD). However, miR-106b-5p expression in the human nucleus pulposus (NP) and potential mechanisms remain to be elucidated. In this study, the aim was to verify the potential therapeutic mechanisms of miR-106b-5p for IDD. Key miRNAs were screened for in degenerative and normal human intervertebral disc samples. qRT-PCR and fluorescence in situ hybridization (FISH) were used to verify the miR-106b-5p differential expression. The targeting link between miR-106b-5p and Sirtuin 2 (SIRT2) was identified using the luciferase reporter assay and bioinformatics. Flow cytometry, EdU method, and cell scratching were all performed to determine the NP cell function and IDD models were constructed for in vivo experiments. SIRT2, MMP13, ADAMTS5, Col II, Aggrecan, Ras, ERK1/2, and p-ERK1/2 protein levels were assayed by western blotting. Overexpression of miR-106b-5p in NP cells decreased cell growth, induced apoptosis, hindered extracellular matrix formation, and increased the expression of matrix-degrading enzymes through the SIRT2/MAPK/ERK signaling pathway. Importantly, intradiscal delivery of antagomiR-106b-5p significantly attenuated IDD development. Our findings demonstrate that targeting miR-106b-5p in intervertebral disc has therapeutic effects on IDD. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Meng, Dihua AU - Meng D AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Chen, Weiyou AU - Chen W AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Pan, Cheng AU - Pan C AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Yang, Kunxue AU - Yang K AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Guan, Yewen AU - Guan Y AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Wang, Jiaqi AU - Wang J AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Moro, Abu AU - Moro A AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Wei, Qingjun AU - Wei Q AD - Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. FAU - Jiang, Hua AU - Jiang H AD - Division of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, 530021, Nanning, Guangxi Zhuang Autonomous Region, China. jianghua@gxmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221029 PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - EC 3.5.1.- (Sirtuin 2) RN - 0 (MicroRNAs) SB - IM MH - Humans MH - *Intervertebral Disc Degeneration/pathology MH - In Situ Hybridization, Fluorescence MH - Sirtuin 2/genetics MH - Apoptosis MH - *MicroRNAs/genetics MH - *Intervertebral Disc/metabolism OTO - NOTNLM OT - Intervertebral disc degeneration OT - MAPK OT - Sirtuin 2 OT - miR-106b-5p EDAT- 2022/10/30 06:00 MHDA- 2023/03/03 06:00 CRDT- 2022/10/29 11:18 PHST- 2022/09/17 00:00 [accepted] PHST- 2022/10/30 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2022/10/29 11:18 [entrez] AID - 10.1007/s10495-022-01773-6 [pii] AID - 10.1007/s10495-022-01773-6 [doi] PST - ppublish SO - Apoptosis. 2023 Feb;28(1-2):199-209. doi: 10.1007/s10495-022-01773-6. Epub 2022 Oct 29.