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衰老小鼠椎间盘内的巨噬细胞变化与高通量测序

Macrophage Changes and High-Throughput Sequencing in Aging Mouse Intervertebral Disks.

作者信息

Wang Wei, Jiang Cheng, Chen Jiong-Hui, Chen Yong-Long, Zhang Zhen-Wu, Yang Zhi-Chao, Li Jun, Li Xiao-Chuan

机构信息

Chongqing Tongnan Hospital of Traditional Chinese Medicine Chongqing People's Republic of China.

Department of Orthopaedic Surgery Gaozhou People's Hospital Gaozhou Guangdong Province People's Republic of China.

出版信息

JOR Spine. 2025 Apr 8;8(2):e70061. doi: 10.1002/jsp2.70061. eCollection 2025 Jun.

DOI:10.1002/jsp2.70061
PMID:40201536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11977178/
Abstract

BACKGROUND

Intervertebral disk (IVD) degeneration is associated with lower back pain and aging; however, the mechanisms underlying age-related changes and the changes in macrophage polarization in aging intervertebral disks require further elucidation. The aim of this study was to evaluate changes in macrophages, the differential expression of senescence genes, and their relationship with hub genes in IVDs during aging in mice.

METHODS

Twenty-eight male wild C57 mice aged 4 weeks were divided into two groups. Four mice per group were selected for high-throughput sequencing and 10 for tail IVD immunohistochemical analysis. Adult and aged mouse IVD specimens were stained with hematoxylin-eosin, Fast Green, and Alcian Blue to determine collagen (Col) 1, Col2, proteoglycan, P16, P21, P53, CD11b, CD86, CD206, IL-1, TGF-β, and IL-4 expression. High-throughput sequencing was performed on adult and aged mouse IVD tissues.

RESULTS

Aged mouse IVDs showed reduced height and marked degeneration, with decreased Col2 and proteoglycan expression and increased Col1 expression. The expression of senescence markers, senescence-associated IL-1, TGF-β, and IL-4, and macrophage-related markers, CD11b, CD86, and CD206, increased markedly with age. High-throughput sequencing revealed 1975 differentially expressed genes in adult and aged mice, with 797 genes showing upregulated expression (top five: , , , , and ) and 1178 showing downregulated expression (top five: , , , , and ). Gene Ontology and pathway enrichment analyses highlighted aging-related cellular components, biological processes, and metabolic pathways. The identified hub genes included , , and .

CONCLUSIONS

Disk senescence and reduced height in aged mice are linked to upregulated expression of senescence-associated phenotypes and macrophage polarization markers. These findings suggest that macrophages and differential gene expression play key roles in age-related IVD degeneration, indicating that they can be used as potential targets for therapeutic intervention.

摘要

背景

椎间盘（IVD）退变与下腰痛和衰老相关；然而，衰老相关变化的潜在机制以及衰老椎间盘中巨噬细胞极化的变化仍需进一步阐明。本研究的目的是评估小鼠衰老过程中IVD内巨噬细胞的变化、衰老基因的差异表达及其与枢纽基因的关系。

方法

将28只4周龄的雄性野生C57小鼠分为两组。每组选取4只小鼠进行高通量测序，10只进行尾部IVD免疫组织化学分析。对成年和老年小鼠的IVD标本进行苏木精-伊红、固绿和阿尔辛蓝染色，以确定胶原蛋白（Col）1、Col2、蛋白聚糖、P16、P21、P53、CD11b、CD86、CD206、白细胞介素-1（IL-1）、转化生长因子-β（TGF-β）和白细胞介素-4（IL-4）的表达。对成年和老年小鼠的IVD组织进行高通量测序。

结果

老年小鼠的IVD高度降低且明显退变，Col2和蛋白聚糖表达减少，Col1表达增加。衰老标志物、衰老相关的IL-1、TGF-β和IL-4以及巨噬细胞相关标志物CD11b、CD86和CD206的表达随年龄显著增加。高通量测序显示成年和老年小鼠中有1975个差异表达基因，其中797个基因表达上调（前五个： ， ， ， ，和 ），1178个基因表达下调（前五个： ， ， ， ，和 ）。基因本体论和通路富集分析突出了与衰老相关的细胞成分、生物学过程和代谢途径。鉴定出的枢纽基因包括 ， 和 。

结论

老年小鼠椎间盘衰老和高度降低与衰老相关表型和巨噬细胞极化标志物的表达上调有关。这些发现表明巨噬细胞和差异基因表达在与年龄相关的IVD退变中起关键作用，表明它们可用作治疗干预的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/fefe274849d4/JSP2-8-e70061-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/2a07d5db54f1/JSP2-8-e70061-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/020787e7c937/JSP2-8-e70061-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/bb766d5b5021/JSP2-8-e70061-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/0a78d5befe84/JSP2-8-e70061-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/ba04a018d946/JSP2-8-e70061-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/fefe274849d4/JSP2-8-e70061-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/2a07d5db54f1/JSP2-8-e70061-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/020787e7c937/JSP2-8-e70061-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/bb766d5b5021/JSP2-8-e70061-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/0a78d5befe84/JSP2-8-e70061-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/ba04a018d946/JSP2-8-e70061-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035a/11977178/fefe274849d4/JSP2-8-e70061-g002.jpg

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