PMID- 36125665 OWN - NLM STAT- MEDLINE DCOM- 20221101 LR - 20221122 IS - 1573-675X (Electronic) IS - 1360-8185 (Linking) VI - 27 IP - 11-12 DP - 2022 Dec TI - Orientin downregulating oxidative stress-mediated endoplasmic reticulum stress and mitochondrial dysfunction through AMPK/SIRT1 pathway in rat nucleus pulposus cells in vitro and attenuated intervertebral disc degeneration in vivo. PG - 1031-1048 LID - 10.1007/s10495-022-01770-9 [doi] AB - Although considered as a major contributor to low back pain (LBP), intervertebral disc degeneration (IVDD) has poor medical and surgical treatments. Various studies have revealed that endoplasmic reticulum (ER) stress and extracellular matrix (ECM) degeneration play a vital role in initiating and developing the progression of IVDD. Moreover, restoration of SIRT1/AMPK was confirmed to prevent IVDD and damage via maintaining ER and extracellular homeostasis. In addition, orientin (Ori) has been shown to upregulate SIRT1. However, the effect of Ori in nucleus pulposus cells (NPCs) is not determined. Hence, in this study we aim to explore the function of Ori in IVDD pathological model. The results demonstrate that Ori treatment in vitro increased SIRT1/AMPK in NPCs, maintained ECM and ER balance and decreased oxidative stress (OS) response. Ori rescued the disordered homeostasis stimulated by tert-butyl hydroperoxide (TBHP), and its function can be inhibited by thapsigargin (TG). Compound C and EX-527, inhibitors of AMPK and SIRT1 counteracted the Ori-mediated ER stress elimination. These results confirm that Ori exerts its effects by upregulating AMPK and SIRT1. Puncture-stimulated IVDD rats were used to show that Ori attenuates the pathological development in vivo. In all, we partly unveil the underlying mechanisms of Ori in IVDD. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Zhang, Zhao AU - Zhang Z AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Wu, Jingtao AU - Wu J AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Teng, Cheng AU - Teng C AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Wang, Jinquan AU - Wang J AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Yu, Jiapei AU - Yu J AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Jin, Chen AU - Jin C AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Wang, Libo AU - Wang L AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Wu, Long AU - Wu L AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Lin, Zhen AU - Lin Z AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Yu, Ziping AU - Yu Z AD - Wenzhou Key Laboratory for Virology and Immunology, Institute of Virology, Wenzhou University, Wenzhou, 325035, Zhejiang, China. FAU - Lin, Zhongke AU - Lin Z AD - Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. zhongkelinspine@163.com. AD - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. zhongkelinspine@163.com. AD - The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. zhongkelinspine@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220920 PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - EC 3.5.1.- (Sirtuin 1) RN - IAX93XCW6C (orientin) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.5.1.- (Sirt1 protein, rat) SB - IM MH - Rats MH - Animals MH - *Nucleus Pulposus/metabolism MH - *Intervertebral Disc Degeneration/genetics/pathology MH - Sirtuin 1/genetics/metabolism MH - Endoplasmic Reticulum Stress MH - AMP-Activated Protein Kinases/genetics/metabolism MH - Rats, Sprague-Dawley MH - Apoptosis MH - Oxidative Stress MH - Mitochondria MH - *Intervertebral Disc/metabolism/pathology OTO - NOTNLM OT - AMPK/SIRT1 OT - Endoplasmic reticulum stress OT - Intervertebral disc degeneration OT - Orientin OT - Oxidative stress OT - Tert-butyl hydroperoxide EDAT- 2022/09/21 06:00 MHDA- 2022/11/02 06:00 CRDT- 2022/09/20 11:20 PHST- 2022/08/28 00:00 [accepted] PHST- 2022/09/21 06:00 [pubmed] PHST- 2022/11/02 06:00 [medline] PHST- 2022/09/20 11:20 [entrez] AID - 10.1007/s10495-022-01770-9 [pii] AID - 10.1007/s10495-022-01770-9 [doi] PST - ppublish SO - Apoptosis. 2022 Dec;27(11-12):1031-1048. doi: 10.1007/s10495-022-01770-9. Epub 2022 Sep 20.