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CD44 通过 Smad 和 ERK 信号通路对人羊膜间充质干细胞向软骨细胞分化的影响。

Effect of CD44 on differentiation of human amniotic mesenchymal stem cells into chondrocytes via Smad and ERK signaling pathways.

机构信息

Zunyi Municipal Key Laboratory of Medicinal Biotechnology, Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.

Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China.

出版信息

Mol Med Rep. 2020 Jun;21(6):2357-2366. doi: 10.3892/mmr.2020.11044. Epub 2020 Mar 30.

Abstract

CD44 antigen (CD44) is a transmembrane protein found in cell adhesion molecules and is involved in the regulation of various physiological processes in cells. It was hypothesized that CD44 directly affected the chondrogenic differentiation of human amniotic mesenchymal stem cells (hAMSCs). In the present study, the expression of chondrocyte‑associated factors was detected in the absence and presence of the antibody blocker anti‑CD44 antibody during the chondrogenic differentiation of hAMSCs. Following inhibition of CD44 expression, the transcriptional levels of chondrocyte‑associated genes SRY‑box transcription factor 9, aggrecan and collagen type II α 1 chain, as well as the production of chondrocyte markers type II collagen and aggrecan were significantly decreased in hAMSCs. Further investigation indicated that there was no significant change in total ERK1/2 expression following inhibition of CD44 expression; however, phosphorylated (p)‑ERK1/2 expression was decreased. The expression of p‑Smad2/3 was also upregulated following CD44 inhibition. These data indicated that CD44 may affect the differentiation of hAMSCs into chondrocytes by regulating the Smad2/3 and ERK1/2 signaling pathway.

摘要

CD44 抗原(CD44)是一种存在于细胞黏附分子中的跨膜蛋白,参与细胞中各种生理过程的调节。据推测,CD44 直接影响人羊膜间充质干细胞(hAMSCs)的软骨分化。在本研究中,在 hAMSCs 软骨分化过程中,检测了缺乏和存在抗体阻断剂抗 CD44 抗体时与软骨细胞相关的因子的表达。抑制 CD44 表达后,hAMSCs 中与软骨细胞相关的基因 SRY-box 转录因子 9、聚集蛋白聚糖和 II 型胶原 α1 链的转录水平以及软骨细胞标志物 II 型胶原和聚集蛋白聚糖的产生均显著降低。进一步研究表明,抑制 CD44 表达后 ERK1/2 的总表达没有明显变化;然而,磷酸化(p)ERK1/2 的表达减少。CD44 抑制后 p-Smad2/3 的表达也上调。这些数据表明,CD44 可能通过调节 Smad2/3 和 ERK1/2 信号通路影响 hAMSCs 向软骨细胞的分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3704/7185282/826b9a278ed5/MMR-21-06-2357-g00.jpg

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