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.
Highlights
Intervertebral disc degeneration (IDD) is a disease of discs that connect adjoining vertebrae, in which structural damage causes the degeneration of the disc and the surrounding area
To explore whether IGFBP5 exerts its effects through the Extracellular signal‐regulated kinase (ERK) signalling pathway, which contributes to nucleus pulposus (NP) cell proliferation and survival, we performed quantitative real‐time PCR (qRT‐PCR) and Western blot analyses to examine the levels of several genes and related pro‐ teins, including ERK, pERK, Bax, caspase‐3 and Bcl[2]
To further investigate the role of IGFBP5 in the pathogenesis of IDD, we performed functional anal‐ ysis of IGFBP5 to investigate the relationship between IGFBP5 and NP cell proliferation and apoptosis
Summary
Intervertebral disc degeneration (IDD) is a disease of discs that connect adjoining vertebrae, in which structural damage causes the degeneration of the disc and the surrounding area This disease is a common cause of back pain in patients who do not achieve im‐ provement with conservative management that possibly requires surgery.[1,2]. The expression of several growth factors and their respective receptors has been reported in areas of degeneration in human and animal intervertebral discs.[4]. A previous study demonstrated that exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways.[13]. We aimed to determine the role of IGFBP5 in NP cell proliferation and apoptosis and the involvement of the ERK sig‐ nalling pathway in this process. The cells from the second passage were used for the subsequent experiments
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