对狗自发性椎间盘退行性病变中的炎症介质进行靶向筛选,发现肿瘤坏死超家族的上调现象

IF 3.4 3区 医学 Q1 ORTHOPEDICS JOR Spine Pub Date : 2023-11-23 DOI:10.1002/jsp2.1292
Thomas Bitterli, David Schmid, Ladina Ettinger, Olga Krupkova, Frances C. Bach, Marianna A. Tryfonidou, Björn P. Meij, Antonio Pozzi, Frank Steffen, Karin Wuertz-Kozak, Lucas A. Smolders
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引用次数: 0

摘要

退化的椎间盘(IVD)和相应的黄韧带(LF)中炎症介质的调控是一个新出现的令人感兴趣的话题。该研究旨在利用自发性椎间盘退行性病变(DDD)的狗模型研究退行性LF和IVD中一系列炎症介质的表达,以确定潜在的治疗靶点。LF和IVD组织取自22只正常狗(Pfirrmann分级I级和II级)和18只受DDD影响的狗(Pfirrmann分级III级和IV级)。使用 qPCR 基因阵列研究了 LF 和 IVD 组织中 80 个炎症基因的表达,然后使用 qPCR、Western 印迹 (WB) 和免疫组织化学方法研究了其他组织样本中感兴趣的靶点。肿瘤坏死因子超家族(TNFSF)信号传导被确定为DDD中受调控的通路,其依据是变性IVD中各种TNFSF成员的显著调控(n-fold ± SD),包括神经生长因子(NGF;-8 ± 10)、CD40LG(464 ± 442)、CD70(341 ± 336)、TNFSF配体10(9 ± 8)和RANKL/TNFSF配体11(85 ± 74)。相反,与对照组相比,变性 LF 中的 TNFSF 基因没有受到明显影响。与对照组相比,退化的LF(4.4 ± 0.5)和IVD(11.3 ± 5.6)中NGF(WB)的蛋白表达均明显上调。在变性晚期(Thompson IV级和V级),RANKL免疫阳性在IVD的髓核和纤维环中明显上调,而在LF中则没有。TNFSF成员在同一个人的多个脊柱组织中的不同参与,为了解DDD所涉及的炎症过程提供了新的视角,并为确定潜在的治疗靶点提供了假说基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Targeted screening of inflammatory mediators in spontaneous degenerative disc disease in dogs reveals an upregulation of the tumor necrosis superfamily

Background

The regulation of inflammatory mediators in the degenerating intervertebral disc (IVD) and corresponding ligamentum flavum (LF) is a topic of emerging interest. The study aimed to investigate the expression of a broad array of inflammatory mediators in the degenerated LF and IVD using a dog model of spontaneous degenerative disc disease (DDD) to determine potential treatment targets.

Methods

LF and IVD tissues were collected from 22 normal dogs (Pfirrmann grades I and II) and 18 dogs affected by DDD (Pfirrmann grades III and IV). A qPCR gene array was used to investigate the expression of 80 inflammatory genes for LF and IVD tissues, whereafter targets of interest were investigated in additional tissue samples using qPCR, western blot (WB), and immunohistochemistry.

Results

Tumor necrosis factor superfamily (TNFSF) signaling was identified as a regulated pathway in DDD, based on the significant regulation (n-fold ± SD) of various TNFSF members in the degenerated IVD, including nerve growth factor (NGF; −8 ± 10), CD40LG (464 ± 442), CD70 (341 ± 336), TNFSF Ligand 10 (9 ± 8), and RANKL/TNFSF Ligand 11 (85 ± 74). In contrast, TNFSF genes were not significantly affected in the degenerated LF compared to the control LF. Protein expression of NGF (WB) was significantly upregulated in both the degenerated LF (4.4 ± 0.5) and IVD (11.3 ± 5.6) compared to the control group. RANKL immunopositivity was significantly upregulated in advanced stages of degeneration (Thompson grades IV and V) in the nucleus pulposus and annulus fibrosus of the IVD, but not in the LF.

Conclusions

DDD involves a significant upregulation of various TNFSF members, with tissue-specific expression profiles in LF and IVD tissues. The differential involvement of TNFSF members within multiple spinal tissues from the same individual provides new insights into the inflammatory processes involved in DDD and may provide a basis to formulate hypotheses for the determination of potential treatment targets.

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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
期刊最新文献
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