人脐带间充质干细胞通过激活 Wnt/β-catenin 信号通路缓解大鼠膝骨关节炎。

Human Umbilical Cord Mesenchymal Stem Cells Alleviate Rat Knee Osteoarthritis via Activating Wnt/ β-catenin Signaling Pathway.

机构信息

Institute of Clinical Pharmacology, Anhui Medical University, Hefei, 230032, China.

Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, 230032, China.

出版信息

Curr Stem Cell Res Ther. 2024;19(2):234-244. doi: 10.2174/1574888X18666230428094400.

DOI:10.2174/1574888X18666230428094400

PMID:37132309

Abstract

BACKGROUND

Osteoarthritis (OA) is a chronic disease characterized by joint cartilage degeneration, destruction, and osteogenic hyperplasia. Human umbilical cord mesenchymal stem cells (hUCMSCs) have attracted increasing research interest due to their high clonogenic, proliferative, and migratory potential, as well as their improved secretion of relevant chondrogenic factors. This study evaluated the therapeutic potential and underlying mechanism of hUC-MSCs in alleviating pathological symptoms of OA.

METHODS

For the study, OA rats were established by the Hulth method to observe the therapeutic effect of intra-articular injection of hUC-MSCs. X-ray tests, gross observations, and histological and immunohistochemical assessments were conducted in rats. Levels of interleukin-1 beta (IL-1β), IL-6, matrix metalloproteinase-13 (MMP-13), and tissue inhibitor matrix metalloproteinase-1 in rats' synovial fluid were measured using enzyme-linked immunosorbent assay kits. For the study, hUC-MSCs and chondrocytes were cultured to explore the effect and underlying mechanisms of hUC-MSCs on OA. Apoptosis, proliferation, and glycosaminoglycan (GAG) were measured in the chondrocytes. The relative expression of aggrecan, , and mRNA was quantified by real-time polymerase chain reaction. Expressions of Wnt/β-catenin signaling molecules were measured by Western blot.

RESULTS

We found that intra-articular injection of hUC-MSCs reduced the combined score, increased the expression of collagen II, and decreased the expression of MMP-13, IL-1β, and IL-6 in rat knee joints. Additionally, hUC-MSCs increased the content of GAGs, inhibited chondrocyte apoptosis, and promoted chondrocyte proliferation. The expression of aggrecan, , and mRNA in chondrocytes was promoted by hUC-MSCs activation of the Wnt/β-catenin signaling pathway.

CONCLUSION

Overall, this study demonstrated that hUC-MSCs induce the secretion of some cytokines the paracrine function to activate the Wnt/β-catenin signaling pathway to reduce the pathological condition of OA and maintain the proper expression of cytokines and extracellular matrix proteins.

摘要

背景

骨关节炎（OA）是一种以关节软骨退变、破坏和骨生成性增生为特征的慢性疾病。人脐带间充质干细胞（hUCMSCs）由于其高克隆形成、增殖和迁移潜力，以及相关软骨生成因子的改善分泌，引起了越来越多的研究兴趣。本研究评估了 hUC-MSCs 缓解 OA 病理症状的治疗潜力和潜在机制。

方法

通过 Hulth 方法建立 OA 大鼠模型，观察关节内注射 hUC-MSCs 的治疗效果。对大鼠进行 X 射线检查、大体观察和组织学及免疫组织化学评估。采用酶联免疫吸附试剂盒检测大鼠关节滑液中白细胞介素 1β（IL-1β）、IL-6、基质金属蛋白酶-13（MMP-13）和组织抑制剂基质金属蛋白酶-1 的水平。体外培养 hUC-MSCs 和软骨细胞，探讨 hUC-MSCs 对 OA 的作用及潜在机制。检测软骨细胞的凋亡、增殖和糖胺聚糖（GAG）。采用实时聚合酶链反应定量检测聚集蛋白聚糖、和 mRNA 的相对表达。采用 Western blot 检测 Wnt/β-catenin 信号分子的表达。

结果

我们发现关节内注射 hUC-MSCs 降低了大鼠膝关节的综合评分，增加了胶原 II 的表达，降低了 MMP-13、IL-1β和 IL-6 的表达。此外，hUC-MSCs 增加了 GAG 含量，抑制了软骨细胞凋亡，促进了软骨细胞增殖。hUC-MSCs 通过激活 Wnt/β-catenin 信号通路促进软骨细胞中聚集蛋白聚糖、和 mRNA 的表达。