title: Role of miR-155 in the regulation of MMP-16 expression in intervertebral disc degeneration.
abstract: The molecular mechanisms of intervertebral disc degeneration (IDD) remain elusive. We found that miR-155 is down-regulated in degenerative nucleus pulposus (NP), and more severe degeneration is correlated with higher matrix metallopeptidase 16 (MMP-16) expression. MMP-16 also degraded matrix aggrecan. Here, we addressed the in vivo miR-155-mediated pathological impact on IDD using a classic puncture mouse model. Lentiviral upregulated-miR-155 or downregulated-miR-155 was transduced into the discs of C57 mice, which was validated by real-time polymerase chain reaction (real-time PCR) and in situ hybridization. Immunohistochemistry and western blotting revealed that up-regulation of miR-155 resulted in down-regulation of MMP-16 and an increase in aggrecan and collagen type II in mouse NP; whereas, down-regulation of miR-155 resulted in up-regulation of MMP-16 and a decrease in aggrecan in mouse NP. Radiographic and histological analysis showed that the up-regulation of miR-155 attenuated IDD, while down-regulation of miR-155 resulted in the deterioration of IDD. These findings indicate that decreased miR-155 contributed to the up-regulation of MMP-16 in vivo, and MMP-16 further degraded aggrecan and collagen type II, leading to the dehydration and degeneration of discs. Our findings revealed a therapeutic role for miR-155 in IDD. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1323-1334, 2017.
authors.affiliation: Department of Orthopedics, The First Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, Liaoning, China.|Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 127 Changle Western Road, Xi'an 710032, China.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Air Force General Hospital, PLA, Beijing, China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, The First Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, Liaoning, China.
authors.forename: Hong-Zheng
authors.initials: HZ
authors.lastname: Meng
authors.affiliation: Department of Orthopaedics, Air Force General Hospital, PLA, Beijing, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Du
authors.affiliation: Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Guan-Nan
authors.initials: GN
authors.lastname: Luan
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 127 Changle Western Road, Xi'an 710032, China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Hospital of China Medical University, 155 North Nanjing Street, Shenyang 110001, Liaoning, China.
authors.forename: Mao-Wei
authors.initials: MW
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 127 Changle Western Road, Xi'an 710032, China.
authors.forename: Zhuo-Jing
authors.initials: ZJ
authors.lastname: Luo
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D024043:Collagen Type II / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D016086:Lentivirus; D053513:Matrix Metalloproteinase 16 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D053674:Aggrecans; D024043:Collagen Type II; C524942:MIRN155 microRNA, human; C507102:MMP16 protein, human; D035683:MicroRNAs; D053513:Matrix Metalloproteinase 16; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: MMP-16; aggrecan; disc degeneration; miR-155; nucleus pulposus