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

Ming-liang Ji, Hua Jiang, Xue-jun Zhang, Pei-liang Shi, Chao Li, Hao Wu, Xiao-tao Wu, Yun-tao Wang, Chen Wang and Jun Lu ()
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Ming-liang Ji: Southeast University
Hua Jiang: The First Affiliated Hospital of Guangxi Medical University
Xue-jun Zhang: Southeast University
Pei-liang Shi: Nanjing University
Chao Li: Southeast University
Hao Wu: Southeast University
Xiao-tao Wu: Southeast University
Yun-tao Wang: Southeast University
Chen Wang: Southeast University
Jun Lu: Southeast University

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07360-1

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