ITGB1 promotes the chondrogenic differentiation of human adipose-derived mesenchymal stem cells by activating the ERK si
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ORIGINAL PAPER
ITGB1 promotes the chondrogenic differentiation of human adipose‑derived mesenchymal stem cells by activating the ERK signaling Simin Luo1 · Qiping Shi2 · Wuji Li1 · Wenrui Wu1 · Zhengang Zha1 Received: 11 February 2020 / Accepted: 8 October 2020 © Springer Nature B.V. 2020
Abstract Adipose-derived mesenchymal stem cell (ADSC) with a high capacity of chondrogenic differentiation was a promising candidate for cartilage defect treatment. This study’s objective is to study the roles of integrin β1 (ITGB1) in regulating ADSC chondrogenic differentiations as well as the underlying mechanisms. The identity of ADSC was confirmed by flow cytometry. ITGB1 gene was overexpressed in human ADSC (hADSC) by transfection with LV003-recombinant plasmids. Gene mRNA and protein levels were examined using quantitative RT-PCR and western blotting, respectively. Differentially expressed mRNAs and proteins were characterized by next-generation RNA sequencing and label-free quantitative proteomics, respectively. ERK signaling and AKT signaling in hADSCs were inhibited by treating with SCH772984 and GSK690693, respectively. ITGB1 gene overexpression substantially increased collagen type II alpha 1 chain (COL2A1), aggrecan (ACAN), and SRY-box transcription factor 9 (SOX9) expression but suppressed collagen type I alpha 1 chain (COL1A1) expression in hADSCs. Next-generation RNA sequencing identified a total of 246 genes differentially expressed in hADSCs by ITGB1 overexpression, such as 183 upregulated and 63 downregulated genes. Label-free proteomics characterized 34 proteins differentially expressed in ITGB1-overexpressing hADSCs. Differentially expressed genes and proteins were enriched by different biological processes such as cell adhesion and differentiation and numerous signaling pathways such as the ERK signaling pathway. ERK inhibitor treatment caused substantially enhanced chondrogenic differentiation in ITGB1-overexpressing hADSCs. ITGB1 promoted the chondrogenic differentiation of human ADSCs via the activation of the ERK signaling pathway. Keywords ITGB1 · Mesenchymal stem cell · hADSC · Chondrogenic differentiation · ERK signaling · Cartilage effect
Introduction Articular cartilages on diarthrodial joint surface have important junction-protecting roles by functioning as low-friction interface for motion and cushioning external impacts (Deng et al. 2016). Cartilage defects, due to trauma, inflammation, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10735-020-09918-0) contains supplementary material, which is available to authorized users. * Zhengang Zha [email protected] 1
Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China
Department of Endocrine, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China
2
aging, and also genetic factors, are common intractable orthopedic disorders, featured by incapacity of self-repair because of poor blood supply in articular cartilage ti
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