Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment

Tendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipo...

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Main Authors: Chang Liu, Jing-wan Luo, Ke-ke Zhang, Long-xiang Lin, Ting Liang, Zong-ping Luo, Yong-qing Zhuang, Yu-long Sun
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/2613821
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author Chang Liu
Jing-wan Luo
Ke-ke Zhang
Long-xiang Lin
Ting Liang
Zong-ping Luo
Yong-qing Zhuang
Yu-long Sun
author_facet Chang Liu
Jing-wan Luo
Ke-ke Zhang
Long-xiang Lin
Ting Liang
Zong-ping Luo
Yong-qing Zhuang
Yu-long Sun
author_sort Chang Liu
collection DOAJ
description Tendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipocytes, chondrocytes, or osteocytes in the degenerative microenvironment of tendinopathy. So in this study, the regulating effects of the degenerative tendon microenvironment on differentiation of TDSCs were investigated. TDSCs were isolated from rat Achilles tendons and were grown on normal and degenerative (prepared by stress-deprived culture) decellularized tendon slices (DTSs). Immunofluorescence staining, H&E staining, real-time PCR, and Western blot were used to delineate the morphology, proliferation, and differentiation of TDSCs in the degenerative microenvironment. It was found that TDSCs were much more spread on the degenerative DTSs than those on normal DTSs. The tenocyte-related markers, COL1 and TNMD, were highly expressed on normal DTSs than the degenerative DTSs. The expression of chondrogenic and osteogenic markers, COL2, SOX9, Runx2, and ALP, was higher on the degenerative DTSs compared with TDSCs on normal DTSs. Furthermore, phosphorylated FAK and ERK1/2 were reduced on degenerative DTSs. In conclusion, this study found that the degenerative tendon microenvironment induced TDSCs to differentiate into chondrogenic and osteogenic lineages. It could be attributed to the cell morphology changes and reduced FAK and ERK1/2 activation in the degenerative microenvironment of tendinopathy.
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spelling doaj-art-345cbc11b1fc48379afc081fa3eae8df2025-02-03T01:10:09ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/26138212613821Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon MicroenvironmentChang Liu0Jing-wan Luo1Ke-ke Zhang2Long-xiang Lin3Ting Liang4Zong-ping Luo5Yong-qing Zhuang6Yu-long Sun7Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, ChinaCenter for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, ChinaCenter for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, ChinaCenter for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, ChinaInstitute of Orthopaedics, Soochow University, Suzhou 215007, ChinaInstitute of Orthopaedics, Soochow University, Suzhou 215007, ChinaShenzhen People’s Hospital, Shenzhen, Guangdong, ChinaCenter for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, ChinaTendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipocytes, chondrocytes, or osteocytes in the degenerative microenvironment of tendinopathy. So in this study, the regulating effects of the degenerative tendon microenvironment on differentiation of TDSCs were investigated. TDSCs were isolated from rat Achilles tendons and were grown on normal and degenerative (prepared by stress-deprived culture) decellularized tendon slices (DTSs). Immunofluorescence staining, H&E staining, real-time PCR, and Western blot were used to delineate the morphology, proliferation, and differentiation of TDSCs in the degenerative microenvironment. It was found that TDSCs were much more spread on the degenerative DTSs than those on normal DTSs. The tenocyte-related markers, COL1 and TNMD, were highly expressed on normal DTSs than the degenerative DTSs. The expression of chondrogenic and osteogenic markers, COL2, SOX9, Runx2, and ALP, was higher on the degenerative DTSs compared with TDSCs on normal DTSs. Furthermore, phosphorylated FAK and ERK1/2 were reduced on degenerative DTSs. In conclusion, this study found that the degenerative tendon microenvironment induced TDSCs to differentiate into chondrogenic and osteogenic lineages. It could be attributed to the cell morphology changes and reduced FAK and ERK1/2 activation in the degenerative microenvironment of tendinopathy.http://dx.doi.org/10.1155/2018/2613821
spellingShingle Chang Liu
Jing-wan Luo
Ke-ke Zhang
Long-xiang Lin
Ting Liang
Zong-ping Luo
Yong-qing Zhuang
Yu-long Sun
Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment
Stem Cells International
title Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment
title_full Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment
title_fullStr Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment
title_full_unstemmed Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment
title_short Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment
title_sort tendon derived stem cell differentiation in the degenerative tendon microenvironment
url http://dx.doi.org/10.1155/2018/2613821
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AT longxianglin tendonderivedstemcelldifferentiationinthedegenerativetendonmicroenvironment
AT tingliang tendonderivedstemcelldifferentiationinthedegenerativetendonmicroenvironment
AT zongpingluo tendonderivedstemcelldifferentiationinthedegenerativetendonmicroenvironment
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