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

摘要: Although the number of patients with intervertebral disc (IVD) degeneration is increasing in aging societies, its etiology and pathogenesis remain elusive there currently no effective treatment to prevent this undesirable condition. The unfolded protein response (UPR) a cellular machinery that plays critical roles handling endoplasmic reticulum (ER) stress, condition caused by accumulation proteins ER lumen. This study aimed elucidate potential role UPR mediated pancreatic kinase (PERK), one major stress sensors mammalian cells, development IVD degeneration. was artificially induced Wister rats percutaneously puncturing coccyx IVDs human were collected from who underwent spinal surgery. Expression target genes elevated degenerative both humans rats. induction annulus fibrosus cells significantly increased transcripts for tumor necrosis factor alpha (TNF-α) interleukin 6 (IL-6) nuclear (NF)-κB pathway-dependent manner. expression TNF-α IL-6 reduced selective PERK inhibitor, GSK2606414, gene silencing against activating transcription 4 (ATF4) transcripts. Our findings indicate pathway causally related degeneration, suggesting may be molecular suppressing changes IVDs. © 2017 Orthopaedic Research Society. Published Wiley Periodicals, Inc. J Orthop Res 36:1334-1345, 2018.