The unfolded protein response mediated by PERK is casually related to the pathogenesis of intervertebral disc degeneration

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Takeshi FujiiMasaya Nakamura

Abstract

Although the number of patients with intervertebral disc (IVD) degeneration is increasing in aging societies, its etiology and pathogenesis remain elusive and there is currently no effective treatment to prevent this undesirable condition. The unfolded protein response (UPR) is a cellular machinery that plays critical roles in handling endoplasmic reticulum (ER) stress, a condition caused by the accumulation of unfolded proteins in the ER lumen. This study aimed to elucidate the potential role of the UPR mediated by pancreatic endoplasmic reticulum kinase (PERK), one of the major ER stress sensors in mammalian cells, in the development of IVD degeneration. IVD degeneration was artificially induced in Wister rats by percutaneously puncturing the coccyx IVDs and human IVDs were collected from patients who underwent spinal surgery. Expression of the UPR target genes was elevated in degenerative IVDs in both humans and rats. The induction of ER stress in annulus fibrosus cells significantly increased the transcripts for tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in a nuclear factor (NF)-κB pathway-dependent manner. The expression of TNF-α and IL-6 was significantly reduced by treatment with a selective PERK inhibi...Continue Reading

References

Jun 4, 2002·Nature Reviews. Molecular Cell Biology·Randal J KaufmanStacey M Arnold
Jun 9, 2004·The Journal of Biological Chemistry·Shiyong WuRandal J Kaufman
Nov 18, 2005·Biochemical and Biophysical Research Communications·Nobuyuki FujitaToshio Suda
Aug 11, 2007·Arthritis Research & Therapy·Christine Lyn Le MaitreAnthony J Freemont
May 22, 2008·Biochemical and Biophysical Research Communications·Nobuyuki FujitaTakeshi Miyamoto
Jul 25, 2008·Nature·Kezhong Zhang, Randal J Kaufman
Jun 11, 2010·American Journal of Physiology. Renal Physiology·Takahisa KawakamiMasaomi Nangaku
Sep 29, 2011·The Orthopedic Clinics of North America·Thijs GrunhagenJill P G Urban
Feb 4, 2012·Neuro-degenerative Diseases·Jeroen J M HoozemansWiep Scheper
Jul 27, 2012·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·Ryo OhtaMitsuo Ochi
Aug 14, 2012·Trends in Molecular Medicine·Abhishek D GargPatrizia Agostinis
Sep 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Keitaro HayashiNaohiko Anzai
Oct 30, 2013·Nature Reviews. Rheumatology·Makarand V Risbud, Irving M Shapiro
Nov 12, 2014·Annual Review of Pathology·Scott A Oakes, Feroz R Papa
Jul 1, 2015·Nature Cell Biology·Claudio HetzScott A Oakes
Nov 7, 2015·Arthritis Research & Therapy·Satoshi SuzukiMorio Matsumoto
Mar 24, 2016·Cellular and Molecular Life Sciences : CMLS·Keisuke HoriuchiHideo Morioka
Jun 28, 2016·Nature Reviews. Immunology·Joep GrootjansRichard S Blumberg

❮ Previous
Next ❯

Citations

Dec 19, 2018·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jian ZhangJianru Wang
Mar 1, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Yuichiro MimaNobuyuki Fujita
Apr 10, 2019·American Journal of Physiology. Endocrinology and Metabolism·Qian GuoNing Gu
Dec 1, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Tatsuya YamamotoNobuyuki Fujita
Oct 1, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christopher J PanebiancoJames C Iatridis

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.