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Nat Commun. 2018 Nov 28;9(1):5051. doi: 10.1038/s41467-018-07360-1.

Preclinical development of a microRNA-based therapy for intervertebral disc degeneration.

Author information

1
Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, 210009, Nanjing, China.
2
Department of Spine Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China.
3
Key Laboratory of Model Animal for Disease Study of Ministry of Education, Model Animal Research Center, Collaborative Innovation Center of Genetics and Development, Nanjing University, Nanjing, 210093, China.
4
Department of Orthopaedic Surgery, Zhongda Hospital, School of Medicine, Southeast University, 210009, Nanjing, China. junlusuper@163.com.

Abstract

Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis. Furthermore, miR-141 KO in mice attenuated spontaneous and surgically induced IDD. Mechanistically, miR-141 promotes IDD development by targeting and depleting SIRT1, a negative regulator of NF-κB pathway. Therapeutically, upregulation or downregulation of miR-141 by nanoparticle delivery in IDD model aggravated or alleviated experimental IDD, respectively. Our findings reveal a novel mechanism by which miR-141, in part, promotes IDD progression by interacting with SIRT1/NF-κB pathway. Blockade of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD.

PMID:
30487517
PMCID:
PMC6262020
DOI:
10.1038/s41467-018-07360-1
[Indexed for MEDLINE]
Free PMC Article

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