2. Academic Validation
  3. 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

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

  • Apoptosis. 2022 Sep 20. doi: 10.1007/s10495-022-01770-9.
Zhao Zhang 1 2 3,  Jingtao Wu 1 2 3,  Cheng Teng 1 2 3,  Jinquan Wang 1 2 3,  Jiapei Yu 1 2 3,  Chen Jin 1 2 3,  Libo Wang 1 2 3,  Long Wu 1 2 3,  Zhen Lin 1 2 3,  Ziping Yu 4,  Zhongke Lin 5 6 7
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2 Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China.
  • 3 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 4 Wenzhou Key Laboratory for Virology and Immunology, Institute of Virology, Wenzhou University, Wenzhou, 325035, Zhejiang, China.
  • 5 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. zhongkelinspine@163.com.
  • 6 Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China. zhongkelinspine@163.com.
  • 7 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. zhongkelinspine@163.com.
PMID: 36125665 DOI: 10.1007/s10495-022-01770-9
Abstract

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.

Keywords

AMPK/SIRT1; Endoplasmic reticulum stress; Intervertebral disc degeneration; Orientin; Oxidative stress; Tert-butyl hydroperoxide.

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