Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

Hu, Bo; Shi, Changgui; Xu, Chen; Cao, Peng; Zhang, Ying; Deng, Lianfu; Chen, Huajiang; Wen, Yan

doi:10.1038/srep21190

Cited by 34 publications

(47 citation statements)

References 58 publications

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“…We observed that human degenerative IVD nucleus pulposus tissues showed down-regulated expression of HO-1, up-regulated expression of P65, and increased apoptosis, and these results were consistent with previous studies [9, 16, 17]. Thus, we hypothesized that HO-1 and NF-κB may play a significant role in the process of NPC apoptosis.…”

Section: Discussionsupporting

confidence: 92%

“…In our study, we observed that the number of apoptotic cells in the IDD group was greater than that in the LVF group. Simultaneously, Bo Hu et al [9] indicated that the expression levels of HO-1 in NP from severe IDD were lower than in those of NP from mild IDD. In our study, the numbers of HO-1-positive cells in the IDD group were significantly decreased compared with the LVF group.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Hu et al [9] reported that HO-1 can attenuate IL-1β-induced alteration of anabolic and catabolic activities in human IDD. These results reveal that HO-1 may play a significant role in the progression of IDD.…”

Section: Introductionmentioning

confidence: 99%

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Hemeoxygenase-1 Suppresses IL-1β-Induced Apoptosis Through the NF-κB Pathway in Human Degenerative Nucleus Pulposus Cells

Zhu

Jiang

Cheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Nucleus pulposus cell (NPC) apoptosis is the main factor in intervertebral disc degeneration (IDD); thus, inhibiting the excessive apoptosis of nucleus pulposus cells may be a potential way to alleviate IDD. The effect of Hemeoxygenase-1 (HO-1) on human NPC apoptosis has never been reported. Our study aimed to investigate the effect and mechanism of HO-1 on apoptosis in human degenerative NPCs. Methods: Nucleus pulposus tissues were collected from patients with lumbar vertebral fracture (LVF) and IDD. The expression of HO-1 and P65 in intervertebral discs was determined using immunohistochemistry and western blot analysis. Apoptosis of human nucleus pulposus cells was quantified by flow cytometric analysis. A recombinant lentiviral vector overexpressing HO-1 and HO-1-siRNA was used to promote or silence the expression of HO-1 in nucleus pulposus cells. The NF-κB inhibitor PDTC was used to inhibit the NF-κB pathway. Results: Our study demonstrated that compared with normal samples, IDD samples showed down-regulation of HO-1 expression and up-regulation of P65 expression. Overexpression of HO-1 inhibited the increase in nucleus pulposus cell apoptosis after IL-1β treatment and simultaneously inhibited the expression of p-P65. Furthermore, after treatment with PDTC, the number of apoptotic cells was significantly decreased with or without overexpression of HO-1. Conclusion: HO-1 might play a significant role in IDD, and HO-1 protected degenerative human NPCs against apoptosis induced by IL-1β through the NF-κB pathway. These findings would aid in the development of novel therapeutic approaches for IDD treatment.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Hemeoxygenase-1 Suppresses IL-1β-Induced Apoptosis Through the NF-κB Pathway in Human Degenerative Nucleus Pulposus Cells

Zhu

Jiang

Cheng

et al. 2018

Cell Physiol Biochem

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“…Cells from NP tissue were extracted according to a previous study [40,41], specimens were minced and incubated with 2 U/mL protease (Pronase; Sigma-Aldrich, St Louis, MO, USA) in serum-free DMEM/F12 medium (Gibco, Grand Island, NY, USA) for 30 min at 37 °C after washing twice in PBS. The digested cells were then incubated with 0.25 mg/mL type II collagenase (Gibco) for 4 h at 37 °C.…”

Section: Isolation Of Nucleus Pulposus Cellsmentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Shi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.

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“…Intriguingly, the results are not always consistent between studies, and such problems can be caused by sample variation or other regional factors. Moreover, recent studies purpose that post-transcription and translational regulation are important ways to affect the gene expression in IDD, add to the complexity of the mechanism network of IDD (14). Thus, more precise global expression data are needed before focusing on the detailed mechanism of each gene.…”

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confidence: 99%

Integrated transcriptome and proteome analyses identifies novel genes and regulatory networks in intervertebral disc degeneration

Luo

Wei

et al. 2019

Preprint

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Background: Intervertebral disc degeneration is a major cause of symptoms like low back pain and neck pain. Many groups have tried to reveal the regulatory network using either transcriptome or proteome profiling technologies, however, the relationship between these differentially expressed proteins and mRNAs are not elucidated. Since post-transcriptional regulation and other mechanisms may affect the translation of mRNA to protein, a combined transcriptome and proteome study may give more precise data on unveiling important regulatory network and key genes of Intervertebral disc degeneration. Results: In the present study, we used the label-free quantification proteomic approach and identify 656 proteins expressed in either degenerated or normal nucleus pulposus, of which 503 proteins are differentially expressed. Taking advantage of the existing nucleus pulposus transcriptome data, we combine and reanalyze the data and find 105 differentially expressed mRNA between degenerated and normal nucleus pulposus. By comparing these data, only 9 genes show significant changes in both protein and mRNA data, while 6 genes (TNFAIP6, CHI3L1, KRT19, DPT, COL6A2 and COL11A2) show concordant changes in both protein and mRNA level. Further functional analyses show different functions of the altered mRNAs and proteins in degeneration, indicating great difference between protein network and mRNA network. Using the gene co-expression network method, we uncover novel regulatory network and potential genes that may play vital roles in intervertebral disc degeneration by combining protein and mRNA data. Conclusions: This is the first study to identify novel regulatory network of intervertebral disc degeneration using combined analysis of both transcriptome and proteome, which may give new insight into the molecular mechanism of intervertebral disc degeneration.

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Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

Cited by 34 publications

References 58 publications

Hemeoxygenase-1 Suppresses IL-1β-Induced Apoptosis Through the NF-κB Pathway in Human Degenerative Nucleus Pulposus Cells

Hemeoxygenase-1 Suppresses IL-1β-Induced Apoptosis Through the NF-κB Pathway in Human Degenerative Nucleus Pulposus Cells

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Integrated transcriptome and proteome analyses identifies novel genes and regulatory networks in intervertebral disc degeneration

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