High-mobility group box-1 gene, a potent proinflammatory mediators, is upregulated in more degenerated human discs in vivo and its receptor upregulated by TNF-α exposure in vitro

Experimental and Molecular Pathology
Helen E GruberEdward N Hanley

Abstract

Mechanisms which control and enhance proinflammatory cytokine expression during human disc degeneration are still poorly understood. The high-mobility group box-1 gene (HMGB1) produces a protein which can itself act as a cytokine, or can function as a potent proinflammatory mediator. Little is known about expression of HMGB1 in the human disc. Since proinflammatory cytokines increase significantly during human disc degeneration, in this work we hypothesized that HMGB1 may show upregulation with advancing stages of degeneration, and upregulation in cells exposed to TNF-α. Immunohistochemistry was performed to confirm the presence of HMGB1 in the human disc, and human annulus cells were cultured and challenged with 10(3)pM TNF-α for 14days in 3D culture. Cells with positive HMGB1 immunolocalization were abundant in the outer annulus. Molecular analysis of cultured cells showed an 8-fold significant increase in HMGB1 expression in more degenerated Thompson grade V discs compared to healthier grade I/II discs (p=0.033). Human disc tissue was assessed in molecular studies. Herniated specimens showed a 6.3-fold significantly greater expression level than that seen in control specimens (p=0.001). In culture experiments, expression of ...Continue Reading

References

Jul 25, 2012·Journal of Neuroinflammation·Polina FeldmanFletcher A White
Aug 3, 2012·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·H E GruberE N Hanley
Jun 7, 2014·International Journal of Medical Sciences·Helen E GruberEdward N Hanley
Jul 6, 2014·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Marina KlawitterKarin Wuertz

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Citations

Dec 8, 2017·Scientific Reports·Emerson KrockLisbet Haglund
Dec 17, 2015·The Journal of Biological Chemistry·Emerson KrockLisbet Haglund
Oct 3, 2018·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Bhranti S ShahNadeen O Chahine

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