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Resveratrol‐enhanced SIRT1‐mediated osteogenesis in porous endplates attenuates low back pain and anxiety behaviors
Author(s) -
Lv Xiao,
Chen Songfeng,
Gao Feng,
Hu Binwu,
Wang Yongkui,
Ni Shuangfei,
Kou Hongwei,
Song Zongmian,
Qing Xiangcheng,
Wang Shangyu,
Liu Hongjian,
Shao Zengwu
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002524r
Subject(s) - orthopedic surgery , medicine , university hospital , family medicine , surgery
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, SIRT1 OSX −/− 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 SIRT1 OSX −/− 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.