Role of miR‐155 in the regulation of MMP‐16 expression in intervertebral disc degeneration

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.