Down-regulation of Insulin-like Growth Factor Binding Protein 5 is Involved in Intervertebral Disc Degeneration Via the ERK Signalling Pathway

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2019 Jul 11

PMID 31290273

Citations 10

Authors

Zhonghui Chen

Weibing Zhang

Nu Zhang

Yan Zhou

Geliang Hu

Mingdi Xue

Junhua Liu

Yaming Li

Affiliations

Soon will be listed here.

Abstract

It is obvious that epigenetic processes influence the evolution of intervertebral disc degeneration (IDD). However, its molecular mechanisms are poorly understood. Therefore, we tested the hypothesis that IGFBP5, a potential regulator of IDD, modulates IDD via the ERK signalling pathway. We showed that IGFBP5 mRNA was significantly down-regulated in degenerative nucleus pulposus (NP) tissues. IGFBP5 was shown to significantly promote NP cell proliferation and inhibit apoptosis in vitro, which was confirmed by MTT, flow cytometry and colony formation assays. Furthermore, IGFBP5 was shown to exert its effects by inhibiting the ERK signalling pathway. The effects induced by IGFBP5 overexpression on NP cells were similar to those induced by treatment with an ERK pathway inhibitor (PD98059). Moreover, qRT-PCR and Western blot analyses were performed to examine the levels of apoptosis-related factors, including Bax, caspase-3 and Bcl2. The silencing of IGFBP5 up-regulated the levels of Bax and caspase-3 and down-regulated the level of Bcl2, thereby contributing to the development of human IDD. Furthermore, these results were confirmed in vivo using an IDD rat model, which showed that the induction of Igfbp5 mRNA expression abrogated the effects of IGFBP5 silencing on intervertebral discs. Overall, our findings elucidate the role of IGFBP5 in the pathogenesis of IDD and provide a potential novel therapeutic target for IDD.

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Correction to Downregulation of insulin-like growth factor binding protein 5 is involved in intervertebral disc degeneration via the ERK signalling pathway.

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