Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells

The type III transforming growth factor-β (TGF-β) receptor (TβRIII), a coreceptor of the TGF-β superfamily, is known to bind TGF-βs and regulate TGF-β signaling. However, the regulatory roles of TβRIII in TGF-β-induced mesenchymal stem cell (MSC) chondrogenesis have not been explored. The present st...

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Main Authors: Shuhui Zheng, Hang Zhou, Zhuohui Chen, Yongyong Li, Taifeng Zhou, Chengjie Lian, Bo Gao, Peiqiang Su, Caixia Xu
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/4180857
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author Shuhui Zheng
Hang Zhou
Zhuohui Chen
Yongyong Li
Taifeng Zhou
Chengjie Lian
Bo Gao
Peiqiang Su
Caixia Xu
author_facet Shuhui Zheng
Hang Zhou
Zhuohui Chen
Yongyong Li
Taifeng Zhou
Chengjie Lian
Bo Gao
Peiqiang Su
Caixia Xu
author_sort Shuhui Zheng
collection DOAJ
description The type III transforming growth factor-β (TGF-β) receptor (TβRIII), a coreceptor of the TGF-β superfamily, is known to bind TGF-βs and regulate TGF-β signaling. However, the regulatory roles of TβRIII in TGF-β-induced mesenchymal stem cell (MSC) chondrogenesis have not been explored. The present study examined the effect of TβRIII RNA interference (RNAi) on TGF-β3-induced human MSC (hMSC) chondrogenesis and possible signal mechanisms. A lentiviral expression vector containing TβRIII small interfering RNA (siRNA) (SiTβRIII) or a control siRNA (SiNC) gene was constructed and infected into hMSCs. The cells were cultured in chondrogenic medium containing TGF-β3 or control medium. TβRIII RNAi significantly enhanced TGF-β3-induced chondrogenic differentiation of hMSCs, the ratio of type II (TβRII) to type I (TβRI) TGF-β receptors, and phosphorylation levels of Smad2/3 as compared with cells infected with SiNC. An inhibitor of the TGF-β signal, SB431542, not only inhibited TβRIII RNAi-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also inhibited the effects of TβRIII RNAi on TGF-β3-induced chondrogenic differentiation. These results demonstrate that TβRIII RNAi enhances TGF-β3-induced chondrogenic differentiation in hMSCs by activating TGF-β/Smad2/3 signaling. The finding points to the possibility of modifying MSCs by TβRIII knockdown as a potent future strategy for cell-based cartilage tissue engineering.
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spelling doaj-art-294382cd861e41019d7067d2d841fdec2025-08-20T02:03:52ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/41808574180857Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem CellsShuhui Zheng0Hang Zhou1Zhuohui Chen2Yongyong Li3Taifeng Zhou4Chengjie Lian5Bo Gao6Peiqiang Su7Caixia Xu8Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaOral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaResearch Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaThe type III transforming growth factor-β (TGF-β) receptor (TβRIII), a coreceptor of the TGF-β superfamily, is known to bind TGF-βs and regulate TGF-β signaling. However, the regulatory roles of TβRIII in TGF-β-induced mesenchymal stem cell (MSC) chondrogenesis have not been explored. The present study examined the effect of TβRIII RNA interference (RNAi) on TGF-β3-induced human MSC (hMSC) chondrogenesis and possible signal mechanisms. A lentiviral expression vector containing TβRIII small interfering RNA (siRNA) (SiTβRIII) or a control siRNA (SiNC) gene was constructed and infected into hMSCs. The cells were cultured in chondrogenic medium containing TGF-β3 or control medium. TβRIII RNAi significantly enhanced TGF-β3-induced chondrogenic differentiation of hMSCs, the ratio of type II (TβRII) to type I (TβRI) TGF-β receptors, and phosphorylation levels of Smad2/3 as compared with cells infected with SiNC. An inhibitor of the TGF-β signal, SB431542, not only inhibited TβRIII RNAi-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also inhibited the effects of TβRIII RNAi on TGF-β3-induced chondrogenic differentiation. These results demonstrate that TβRIII RNAi enhances TGF-β3-induced chondrogenic differentiation in hMSCs by activating TGF-β/Smad2/3 signaling. The finding points to the possibility of modifying MSCs by TβRIII knockdown as a potent future strategy for cell-based cartilage tissue engineering.http://dx.doi.org/10.1155/2018/4180857
spellingShingle Shuhui Zheng
Hang Zhou
Zhuohui Chen
Yongyong Li
Taifeng Zhou
Chengjie Lian
Bo Gao
Peiqiang Su
Caixia Xu
Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells
Stem Cells International
title Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells
title_full Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells
title_fullStr Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells
title_full_unstemmed Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells
title_short Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells
title_sort type iii transforming growth factor β receptor rna interference enhances transforming growth factor β3 induced chondrogenesis signaling in human mesenchymal stem cells
url http://dx.doi.org/10.1155/2018/4180857
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