Sex differences in the biomechanical and biochemical responses of caudal rat intervertebral discs to injury

IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine Pub Date : 2023-12-09 DOI:10.1002/jsp2.1299
Hagar M. Kenawy, María I. Nuñez, Xóchitl Morales, Lauren E. Lisiewski, Kevin G. Burt, Min Kyu M. Kim, Leonardo Campos, Nadia Kiridly, Clark T. Hung, Nadeen O. Chahine
{"title":"Sex differences in the biomechanical and biochemical responses of caudal rat intervertebral discs to injury","authors":"Hagar M. Kenawy,&nbsp;María I. Nuñez,&nbsp;Xóchitl Morales,&nbsp;Lauren E. Lisiewski,&nbsp;Kevin G. Burt,&nbsp;Min Kyu M. Kim,&nbsp;Leonardo Campos,&nbsp;Nadia Kiridly,&nbsp;Clark T. Hung,&nbsp;Nadeen O. Chahine","doi":"10.1002/jsp2.1299","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP) worldwide. Sexual dimorphism, or sex-based differences, appear to exist in the severity of LBP. However, it is unknown if there are sex-based differences in the inflammatory, biomechanical, biochemical, and histological responses of intervertebral discs (IVDs).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Caudal (Coccygeal/Co) bone-disc-bone motion segments were isolated from multiple spinal levels (Co8 to Co14) of male and female Sprague–Dawley rats. Changes in motion segment biomechanics and extracellular matrix (ECM) biochemistry (glycosaminoglycan [GAG], collagen [COL], water, and DNA content) were evaluated at baseline and in response to chemical insult (lipopolysaccharide [LPS]) or puncture injury ex vivo. We also investigated the contributions of Toll-like receptor (TLR4) signaling on responses to LPS or puncture injury ex vivo, using a small molecule TLR4 inhibitor, TAK-242.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Findings indicate that IVD motion segments from female donors had greater nitric oxide (NO) release in LPS groups compared to male donors. HMGB1 release was increased in punctured discs, but not LPS injured discs, with no sex effect. Although both male and female discs exhibited reductions in dynamic moduli in response to LPS and puncture injuries, dynamic moduli from female donors were higher than male donors across all groups. In uninjured (baseline) samples, a significant sex effect was observed in nucleus pulposus (NP) DNA and water content. Female annulus fibrosus (AF) also had higher DNA, GAG, and COL content (normalized by dry weight), but lower water content than male AF. Additional injury- and sex-dependent effects were observed in AF GAG/DNA and COL/DNA content. Finally, TAK-242 improved the dynamic modulus of female but not male punctured discs.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our findings demonstrate that there are differences in rat IVD motion segments based on sex, and that the response to injury in inflammatory, biomechanical, biochemical, and histological outcomes also exhibit sex differences. TLR4 inhibition protected against loss of mechanical integrity of puncture-injured IVD motion segments, with differences responses based on donor sex.</p>\n </section>\n </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1299","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOR Spine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jsp2.1299","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP) worldwide. Sexual dimorphism, or sex-based differences, appear to exist in the severity of LBP. However, it is unknown if there are sex-based differences in the inflammatory, biomechanical, biochemical, and histological responses of intervertebral discs (IVDs).

Methods

Caudal (Coccygeal/Co) bone-disc-bone motion segments were isolated from multiple spinal levels (Co8 to Co14) of male and female Sprague–Dawley rats. Changes in motion segment biomechanics and extracellular matrix (ECM) biochemistry (glycosaminoglycan [GAG], collagen [COL], water, and DNA content) were evaluated at baseline and in response to chemical insult (lipopolysaccharide [LPS]) or puncture injury ex vivo. We also investigated the contributions of Toll-like receptor (TLR4) signaling on responses to LPS or puncture injury ex vivo, using a small molecule TLR4 inhibitor, TAK-242.

Results

Findings indicate that IVD motion segments from female donors had greater nitric oxide (NO) release in LPS groups compared to male donors. HMGB1 release was increased in punctured discs, but not LPS injured discs, with no sex effect. Although both male and female discs exhibited reductions in dynamic moduli in response to LPS and puncture injuries, dynamic moduli from female donors were higher than male donors across all groups. In uninjured (baseline) samples, a significant sex effect was observed in nucleus pulposus (NP) DNA and water content. Female annulus fibrosus (AF) also had higher DNA, GAG, and COL content (normalized by dry weight), but lower water content than male AF. Additional injury- and sex-dependent effects were observed in AF GAG/DNA and COL/DNA content. Finally, TAK-242 improved the dynamic modulus of female but not male punctured discs.

Conclusions

Our findings demonstrate that there are differences in rat IVD motion segments based on sex, and that the response to injury in inflammatory, biomechanical, biochemical, and histological outcomes also exhibit sex differences. TLR4 inhibition protected against loss of mechanical integrity of puncture-injured IVD motion segments, with differences responses based on donor sex.

Abstract Image

尾部大鼠椎间盘对损伤的生物力学和生物化学反应的性别差异
椎间盘退变(IDD)是世界范围内腰痛(LBP)的主要原因。性二态性,或性别差异,似乎存在于腰痛的严重程度。然而,椎间盘(ivd)的炎症、生物力学、生化和组织学反应是否存在性别差异尚不清楚。从雄性和雌性Sprague-Dawley大鼠的多个脊柱节段(Co8至Co14)中分离出尾侧(尾骨/Co)骨-盘-骨运动节段。运动段生物力学和细胞外基质(ECM)生物化学(糖胺聚糖[GAG]、胶原[COL]、水和DNA含量)的变化在基线和对化学损伤(脂多糖[LPS])或体外穿刺损伤的反应中进行了评估。我们还使用一种小分子TLR4抑制剂TAK - 242研究了Toll样受体(TLR4)信号在LPS或穿刺损伤反应中的作用。研究结果表明,与男性供者相比,LPS组女性供者的IVD运动节段有更多的一氧化氮(NO)释放。HMGB1释放在穿刺椎间盘中增加,而LPS损伤椎间盘中没有增加,无性别影响。尽管男性和女性的椎间盘在LPS和穿刺损伤后都表现出动态模量的减少,但在所有组中,女性供体的动态模量都高于男性供体。在未损伤(基线)样品中,在髓核(NP) DNA和含水量中观察到显著的性别效应。雌性纤维环(AF)也具有更高的DNA、GAG和COL含量(按干重标准化),但含水量低于雄性纤维环。在AF中,GAG/DNA和COL/DNA含量存在额外的损伤和性别依赖效应。最后,TAK‐242改善了女性穿刺椎间盘的动态模量,但没有改善男性穿刺椎间盘的动态模量。我们的研究结果表明,基于性别的大鼠IVD运动节段存在差异,并且对炎症,生物力学,生化和组织学结果的损伤反应也表现出性别差异。TLR4抑制保护了穿刺损伤的IVD运动节段的机械完整性的丧失,基于供体性别的反应不同。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信