Resveratrol-enhanced SIRT1-mediated osteogenesis in porous endplates attenuates low back pain and anxiety behaviors.

Abstract

Low back pain (LBP) is a major clinical problem that lacks effective treatments. The sensory innervation in porous vertebral endplates and anxiety contributes to spinal hyperalgesia. We hypothesized that SIRT1 activator resveratrol alleviates LBP and anxiety via promotion of osteogenesis in the porous endplates. The hyperalgesia and anxiety-related behaviors; sensory innervation, inflammation and porosity of endplates; and osteogenic/osteoclastic factors expression were measured following resveratrol treatment after lumbar spine instability (LSI) surgery. To explore whether resveratrol promotes endplates osteogenesis and thus alleviates LBP through activation of SIRT1 in the osteoprogenitor cells of endplates, SIRT1OSX-/- mice were employed. Additionally, the levels of inflammation markers, phosphorylation of cAMP response element-binding protein (pCREB), and brain-derived neurotrophic factor (BDNF) in hippocampus were evaluated. After 4 or 8 weeks LSI surgery, the mice suffered from hyperalgesia and anxiety, which were efficiently attenuated by resveratrol at 8 weeks. Resveratrol treatment-enhanced osteogenesis and decreased endplates porosities accompanied with the reduction of TNFα, IL-1β, and COX2 levels and CGRP+ nerve fibers innervation in porous endplates. Resveratrol-mediated endplates osteogenesis, decreased endplates porosities, and analgesic and antianxiety effects were abrogated in SIRT1OSX-/- mice. Furthermore, resveratrol relieved inflammation and increased pCREB and BDNF expression in the hippocampus after 8 weeks, which alleviate anxiety-related behaviors. This study provides that resveratrol-mediated porous endplates osteogenesis via the activation of SIRT1 markedly blocked sensory innervation and inflammation in endplates, therefore, alleviating LSI surgery-induced LBP and hippocampus-related anxiety.

• Authors: Xiao Lv, Songfeng Chen, Feng Gao, Binwu Hu, Yongkui Wang, Shuangfei Ni, Hongwei Kou, Zongmian Song, Xiangcheng Qing, Shangyu Wang, Hongjian Liu, Zengwu Shao
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 35 Issue 3 Pg. e21414 (03 2021) ISSN: 1530-6860 [Electronic] United States
• PMID: 33583095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

Chemical References

• Anti-Anxiety Agents
• Sirt1 protein, mouse
• Sirtuin 1
• Resveratrol

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Anxiety (drug therapy, metabolism)
• Behavior, Animal (drug effects, physiology)
• Hippocampus (drug effects, metabolism)
• Low Back Pain (drug therapy, metabolism)
• Male
• Mice, Inbred C57BL
• Osteoclasts (drug effects, metabolism)
• Osteogenesis (drug effects)
• Resveratrol (pharmacology)
• Sirtuin 1 (drug effects)
• Mice