MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2

Abstract Background Tendons are a crucial component of the musculoskeletal system and responsible for transmission forces derived from muscle to bone. Patients with tendon injuries are often observed with decreased collagen production and matrix degeneration, and healing of tendon injuries remains a...

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Main Authors: Yang Liu, Lu Feng, Jia Xu, Zhengmeng Yang, Tianyi Wu, Jiajun Zhang, Liu Shi, Dahai Zhu, Jinfang Zhang, Gang Li
Format: Article
Language:English
Published: BMC 2019-03-01
Series:Stem Cell Research & Therapy
Online Access:http://link.springer.com/article/10.1186/s13287-019-1216-y
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author Yang Liu
Lu Feng
Jia Xu
Zhengmeng Yang
Tianyi Wu
Jiajun Zhang
Liu Shi
Dahai Zhu
Jinfang Zhang
Gang Li
author_facet Yang Liu
Lu Feng
Jia Xu
Zhengmeng Yang
Tianyi Wu
Jiajun Zhang
Liu Shi
Dahai Zhu
Jinfang Zhang
Gang Li
author_sort Yang Liu
collection DOAJ
description Abstract Background Tendons are a crucial component of the musculoskeletal system and responsible for transmission forces derived from muscle to bone. Patients with tendon injuries are often observed with decreased collagen production and matrix degeneration, and healing of tendon injuries remains a challenge as a result of limited understanding of tendon biology. Recent studies highlight the contribution of miR-378a on the regulation gene expression during tendon differentiation. Methods We examined the tendon microstructure and tendon repair with using miR-378a knock-in transgenic mice, and the tendon-derived stem cells were also isolated from transgenic mice to study their tenogenic differentiation ability. Meanwhile, the expression levels of tenogenic markers were also examined in mouse tendon-derived stem cells transfected with miR-378a mimics during tenogenic differentiation. With using online prediction software and luciferase reporter assay, the binding target of miR-378a was also studied. Results Our results indicated miR-378a impairs tenogenic differentiation and tendon repair by inhibition collagen and extracellular matrix production both in vitro and in vivo. We also demonstrated that miR-378a exert its inhibitory role during tenogenic differentiation through binding at TGFβ2 by luciferase reporter assay and western blot. Conclusions Our investigation suggests that miR-378a could be considered as a new potential biomarker for tendon injury diagnosis or drug target for a possible therapeutic approach in future clinical practice.
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spelling doaj.art-9dbe43939ae9452696f41779afd6e05f2022-12-22T00:39:27ZengBMCStem Cell Research & Therapy1757-65122019-03-011011910.1186/s13287-019-1216-yMiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2Yang Liu0Lu Feng1Jia Xu2Zhengmeng Yang3Tianyi Wu4Jiajun Zhang5Liu Shi6Dahai Zhu7Jinfang Zhang8Gang Li9Department of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongThe State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical CollegeKey Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese MedicineDepartment of Orthopaedics and Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong KongAbstract Background Tendons are a crucial component of the musculoskeletal system and responsible for transmission forces derived from muscle to bone. Patients with tendon injuries are often observed with decreased collagen production and matrix degeneration, and healing of tendon injuries remains a challenge as a result of limited understanding of tendon biology. Recent studies highlight the contribution of miR-378a on the regulation gene expression during tendon differentiation. Methods We examined the tendon microstructure and tendon repair with using miR-378a knock-in transgenic mice, and the tendon-derived stem cells were also isolated from transgenic mice to study their tenogenic differentiation ability. Meanwhile, the expression levels of tenogenic markers were also examined in mouse tendon-derived stem cells transfected with miR-378a mimics during tenogenic differentiation. With using online prediction software and luciferase reporter assay, the binding target of miR-378a was also studied. Results Our results indicated miR-378a impairs tenogenic differentiation and tendon repair by inhibition collagen and extracellular matrix production both in vitro and in vivo. We also demonstrated that miR-378a exert its inhibitory role during tenogenic differentiation through binding at TGFβ2 by luciferase reporter assay and western blot. Conclusions Our investigation suggests that miR-378a could be considered as a new potential biomarker for tendon injury diagnosis or drug target for a possible therapeutic approach in future clinical practice.http://link.springer.com/article/10.1186/s13287-019-1216-y
spellingShingle Yang Liu
Lu Feng
Jia Xu
Zhengmeng Yang
Tianyi Wu
Jiajun Zhang
Liu Shi
Dahai Zhu
Jinfang Zhang
Gang Li
MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2
Stem Cell Research & Therapy
title MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2
title_full MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2
title_fullStr MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2
title_full_unstemmed MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2
title_short MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2
title_sort mir 378a suppresses tenogenic differentiation and tendon repair by targeting at tgf β2
url http://link.springer.com/article/10.1186/s13287-019-1216-y
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