Significant association of TNF-α, but not other pro-inflammatory cytokines, single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population

Abdollahzade, Sina; Hanaei, Sara; Sadr, Maryam; Mirbolouk, Mohammad Hossein; Fattahi, Ehsan; Rezaei, Nima; Khoshnevisan, Alireza

doi:10.1016/j.clineuro.2018.08.008

Cited by 22 publications

(24 citation statements)

References 27 publications

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“…In the degenerative disc tissue samples, lots of inflammatory cytokines including TNF-α, IL-1β, and IL-17 are found to be increased [ 6–9 ]. Previously, inflammation cytokines were proved to play an important role in regulating disc cell biology and disc matrix metabolism [ 10–13 ]. Importantly, several studies have demonstrated that inflammation cytokines can promote disc cell death [ 14–16 ].…”

Section: Introductionmentioning

confidence: 99%

Osteogenic protein-1 inhibits nucleus pulposus cell apoptosis through regulating the NF-κB/ROS pathway in an inflammation environment

Liu

et al. 2018

Bioscience Reports

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Background: Intervertebral disc degeneration is a pathological process that involves an inflammation response. As a classical cellular feature, several studies have demonstrated that inflammation can promote nucleus pulposus (NP) cell apoptosis. Therefore, attenuation of NP cell apoptosis may be a potential way to retard disc degeneration.Objective: The present study was aimed to investigate the protective effects of osteogenic protein-1 (OP-1) against NP cell apoptosis in an inflammation environment, and the potential signaling transduction pathway.Methods: Rat NP cells were cultured in medium with or without inflammatory cytokine tumor necrosis factor (TNF)-α for 6 days. The exogenous TNF-α was added into the medium to investigate its protective effects. NP cell apoptosis was evaluated by cell apoptosis ratio, caspase-3 activity, gene/protein expression of apoptosis-related molecules (Bcl-2, Bax, and caspase-3). Additionally, the intracellular reactive oxygen species (ROS) content and activity of the NF-κB pathway were also analyzed.Results: Compared with the control NP cells, TNF-α significantly increased cell apoptosis ratio, caspase-3 activity, gene/protein expression of Bcl-2, Bax and caspase-3, ROS content, and activity of the NF-κB pathway. However, OP-1 partly attenuated these effects in NP cells treated with TNF-α.Conclusion: OP-1 is effective in attenuating TNF-α-caused NP cell apoptosis, and the ROS/NF-κB pathway may be the potential signaling transduction pathway. The present study indicates that OP-1 may be helpful to inhibit inflammation-mediated disc degeneration.

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Section: Introductionmentioning

confidence: 99%

Osteogenic protein-1 inhibits nucleus pulposus cell apoptosis through regulating the NF-κB/ROS pathway in an inflammation environment

Liu

et al. 2018

Bioscience Reports

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“…This may lead to inflate the chance of a false positive association. More importantly, three genetic studies focusing on this topic were published in recent years [23][24][25], which were not included in Wang's study. Based on the Cochrane guidelines[30], an overlapping meta-analysis is necessary to be updated in time with latest studies.…”

Section: Discussionmentioning

confidence: 99%

Gene locus polymorphisms and expression levels of interleukin-1 in lumbar disc disease: a meta-analysis and immunohistochemical study

Jiang

Xiao

Zhang

et al. 2020

Preprint

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Background To investigate the association between interleukin (IL)-1α (rs1800587), IL-1β (rs1143634) and IL-1RN variable number tandem repeat (VNTR) polymorphisms, expression levels and lumbar disc disease (LDD). Methods All relevant articles were searched from 4 databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). Odds ratios (OR) with 95% conﬁdence intervals (CI) were calculated to evaluate the association between IL-1 gene locus polymorphisms (rs1800587 in IL-1α, rs1143634 in IL-1β, VNTR in IL-1RN) and LDD susceptibility. Statistical analysis was conducted by Review Manager (Revman) 5.31 software. Furthermore, qRT-PCR and immunohistochemistry (IHC) were performed to evaluate IL-1α, IL-1β and IL-1RN expressions in the normal and degenerated disc. Results A total of 15 case-control studies (1455 cases and 2362 controls) were included in our meta-analysis. The pooled results suggested that IL-1α rs1800587 polymorphism was associated with an increased risk of LDD in overall population (T vs. C, OR=1.21, 95%CI=1.04-1.40, P=0.01). The subgroup analysis found a significant association between IL-1β rs1143634 polymorphism and LDD in Asian population (T vs. C, OR=0.61, 95%CI=0.39-0.96, P=0.03). Results of qRT-PCR and IHC demonstrated that expressions of IL-1α and IL-1-β were significantly increased in the degenerated disc. (all P<0.05) Conclusion IL-1α rs1800587 and IL-1β rs1143634 polymorphisms were significantly associated with LDD in overall population and in Asian population, respectively. The increased expression levels of IL-1α and IL-1β may be the important risk factors for LDD.

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“…This may lead to in ate the chance of a false positive association. More importantly, three genetic studies focusing on this topic were published in recent years [23][24][25], which were not included in Wang's study. Based on the Cochrane guidelines [30], an overlapping meta-analysis is necessary to be updated in time with latest studies.…”

Section: Discussionmentioning

confidence: 99%

“…The most widely studied of these are IL-1α rs1800587, IL-1β rs1143634 polymorphisms and variable number tandem repeat polymorphism (VNTR) of the IL-1RN gene. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] In 2004, Solovieva et al rst reported that IL-1α rs1800587 and IL-1β rs1143634 polymorphisms were associated with LDD risk in a Caucasian population [11]. The association of the IL-1α rs1800587 polymorphism to LDD was subsequently con rmed in Finnish and Danish population studies [15,16].…”

Section: Introductionmentioning

confidence: 99%

Gene locus polymorphisms and expression levels of interleukin-1 in lumbar disc disease: a meta-analysis and immunohistochemical study

Jiang

Xiao

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: To investigate the association between interleukin (IL)-1α (rs1800587), IL-1β (rs1143634) and IL-1 receptor antagonist (RN) variable number tandem repeat (VNTR) polymorphisms, expression levels and lumbar disc disease (LDD).Methods: All relevant articles were searched from 4 databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). Odds ratios (OR) with 95 % conﬁdence intervals (CI) were calculated to evaluate the association between IL-1 gene locus polymorphisms (rs1800587 in IL-1α, rs1143634 in IL-1β, VNTR in IL-1RN) and LDD susceptibility. Statistical analysis was conducted by Review Manager (Revman) 5.31 software. Furthermore, qRT-PCR and immunohistochemistry (IHC) were performed to evaluate IL-1α, IL-1β and IL-1RN expressions in the normal and degenerated disc.Results: A total of 15 case-control studies (1455 cases and 2362 controls) were included in our meta-analysis. The pooled results suggested that IL-1α rs1800587 polymorphism was associated with an increased risk of LDD in overall population (T vs. C, OR=1.21, 95%CI=1.04-1.40, P=0.01). The subgroup analysis found a significant association between IL-1β rs1143634 polymorphism and LDD in Asian population (T vs. C, OR=0.61, 95%CI=0.39-0.96, P=0.03). Results of qRT-PCR and IHC demonstrated that expressions of IL-1α and IL-1-β were significantly increased in the degenerated disc. (all P<0.05 )Conclusion: IL-1α rs1800587 and IL-1β rs1143634 polymorphisms were significantly associated with LDD in overall population and in Asian population, respectively.

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Significant association of TNF-α, but not other pro-inflammatory cytokines, single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population

Cited by 22 publications

References 27 publications

Osteogenic protein-1 inhibits nucleus pulposus cell apoptosis through regulating the NF-κB/ROS pathway in an inflammation environment

Osteogenic protein-1 inhibits nucleus pulposus cell apoptosis through regulating the NF-κB/ROS pathway in an inflammation environment

Gene locus polymorphisms and expression levels of interleukin-1 in lumbar disc disease: a meta-analysis and immunohistochemical study

Gene locus polymorphisms and expression levels of interleukin-1 in lumbar disc disease: a meta-analysis and immunohistochemical study

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