MSC-derived exosomes promote chondrocyte proliferation and inhibit apoptosis by suppressing inflammation in osteoarthritis

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-09-25 DOI:10.1016/j.tice.2025.103157

Chaochao Ji , Wendan Cheng

{"title":"MSC-derived exosomes promote chondrocyte proliferation and inhibit apoptosis by suppressing inflammation in osteoarthritis","authors":"Chaochao Ji , Wendan Cheng","doi":"10.1016/j.tice.2025.103157","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is marked by reduced chondrocyte proliferation, increased apoptosis, and an inflammatory microenvironment. Mesenchymal stem cell-derived exosomes (MSC-Exos) are promising modulators of chondrocyte function; however, their precise roles remain unclear. This study explores whether MSC-Exos protect chondrocytes from IL-1β-induced injury via these effects, in vitro and in a rat OA model.</div></div><div><h3>Methods</h3><div>BMSC-derived exosomes (BMSC-Exos) were isolated via ultracentrifugation and characterized (TEM, NTA, Western blotting). Chondrocyte injury was induced by IL-1β (10 ng/mL). Effects of BMSC-Exos on proliferation (CCK-8), apoptosis (Annexin V/PI), migration (wound healing/Transwell), inflammatory cytokines (ELISA), and NF-κB p65 phosphorylation (Western blotting) were evaluated. <em>In vivo</em>, OA was induced by intra-articular sodium iodoacetate in rats, and MSC-Exos were administered weekly. Histological staining (H&E and Safranin O-Fast Green) was performed to assess cartilage repair, immunohistochemical (IHC) analysis for IL-1β, TNF-α, IL-6, type II collagen and aggrecan was conducted, and analysis of p65 phosphorylation in cartilage tissue was conducted.</div></div><div><h3>Results</h3><div>BMSC-Exos significantly increased chondrocyte proliferation, reduced apoptosis, suppressed TNF-α, IL-6, and IL-1β expression, and inhibited p65 phosphorylation <em>in vitro</em>. <em>In vivo</em>, BMSC-Exos attenuated cartilage erosion, subchondral bone exposure, synovial hyperplasia and inflammatory cell infiltration. IHC analysis demonstrated that BMSC-Exos treatment significantly reduced the expression of IL-1β, TNF-α, IL-6, while restoring the levels of cartilage matrix components in cartilage compared to the OA model group. Reduced phospho-p65 levels correlated with these histological and molecular improvements.</div></div><div><h3>Conclusion</h3><div>MSC-Exos protect chondrocytes from inflammatory injury via promoting proliferation, inhibiting apoptosis, reducing inflammation, and suppressing NF-κB, with therapeutic potential for OA.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103157"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816625004392","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Osteoarthritis (OA) is marked by reduced chondrocyte proliferation, increased apoptosis, and an inflammatory microenvironment. Mesenchymal stem cell-derived exosomes (MSC-Exos) are promising modulators of chondrocyte function; however, their precise roles remain unclear. This study explores whether MSC-Exos protect chondrocytes from IL-1β-induced injury via these effects, in vitro and in a rat OA model.

Methods

BMSC-derived exosomes (BMSC-Exos) were isolated via ultracentrifugation and characterized (TEM, NTA, Western blotting). Chondrocyte injury was induced by IL-1β (10 ng/mL). Effects of BMSC-Exos on proliferation (CCK-8), apoptosis (Annexin V/PI), migration (wound healing/Transwell), inflammatory cytokines (ELISA), and NF-κB p65 phosphorylation (Western blotting) were evaluated. In vivo, OA was induced by intra-articular sodium iodoacetate in rats, and MSC-Exos were administered weekly. Histological staining (H&E and Safranin O-Fast Green) was performed to assess cartilage repair, immunohistochemical (IHC) analysis for IL-1β, TNF-α, IL-6, type II collagen and aggrecan was conducted, and analysis of p65 phosphorylation in cartilage tissue was conducted.

Results

BMSC-Exos significantly increased chondrocyte proliferation, reduced apoptosis, suppressed TNF-α, IL-6, and IL-1β expression, and inhibited p65 phosphorylation in vitro. In vivo, BMSC-Exos attenuated cartilage erosion, subchondral bone exposure, synovial hyperplasia and inflammatory cell infiltration. IHC analysis demonstrated that BMSC-Exos treatment significantly reduced the expression of IL-1β, TNF-α, IL-6, while restoring the levels of cartilage matrix components in cartilage compared to the OA model group. Reduced phospho-p65 levels correlated with these histological and molecular improvements.

Conclusion

MSC-Exos protect chondrocytes from inflammatory injury via promoting proliferation, inhibiting apoptosis, reducing inflammation, and suppressing NF-κB, with therapeutic potential for OA.

查看原文本刊更多论文

骨髓间质干细胞衍生的外泌体通过抑制骨关节炎炎症促进软骨细胞增殖和抑制细胞凋亡。

背景：骨关节炎（OA）以软骨细胞增殖减少、细胞凋亡增加和炎症微环境为特征。间充质干细胞衍生外泌体（MSC-Exos）是软骨细胞功能的有前途的调节剂；然而，它们的确切作用仍不清楚。本研究在体外和大鼠OA模型中探讨MSC-Exos是否通过这些作用保护软骨细胞免受il -1β诱导的损伤。方法：采用超离心分离bmsc来源外泌体（BMSC-Exos），并用TEM、NTA、Western blotting对其进行表征。IL-1β（10 ng/mL）诱导软骨细胞损伤。观察BMSC-Exos对细胞增殖（CCK-8）、细胞凋亡（Annexin V/PI）、迁移（创面愈合/Transwell）、炎症因子（ELISA）和NF-κB p65磷酸化（Western blotting）的影响。在体内，大鼠关节内碘乙酸钠诱导OA，每周给药MSC-Exos。组织染色（H&E和Safranin O-Fast Green）评估软骨修复，免疫组化（IHC）分析IL-1β、TNF-α、IL-6、II型胶原和聚集蛋白，分析软骨组织中p65磷酸化。结果：BMSC-Exos能显著促进体外培养的软骨细胞增殖，减少细胞凋亡，抑制TNF-α、IL-6、IL-1β表达，抑制p65磷酸化。在体内，BMSC-Exos减轻了软骨侵蚀、软骨下骨暴露、滑膜增生和炎症细胞浸润。IHC分析显示，与OA模型组相比，BMSC-Exos治疗显著降低了IL-1β、TNF-α、IL-6的表达，同时恢复了软骨中软骨基质成分的水平。磷酸化-p65水平的降低与这些组织学和分子改善相关。结论：MSC-Exos通过促进软骨细胞增殖、抑制细胞凋亡、减轻炎症、抑制NF-κB等机制保护软骨细胞免受炎症损伤，具有治疗骨性关节炎的潜力。

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

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.