MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-\u03b22

Dahai Zhu,Jiajun Zhang,Liu Shi,Gang Li,Zhengmeng Yang,Yang Liu,Lu Feng,Jinfang Zhang,Jia Xu,Tianyi Wu

doi:10.1186/s13287-019-1216-y

Abstract

BackgroundTendons 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.MethodsWe 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.ResultsOur 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.ConclusionsOur 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.

Highlights

Tendons are a crucial component of the musculoskeletal system and responsible for the transmission forces derived from muscle to bone
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 clinical practice
Impaired tendon tissues and delayed tendon injury healing were observed in miR-378a Tg mice In this study, 5 ng/ml TGFβ1 was applied to induce tenogenic differentiation, and our results showed that the collagen production was increased by TGFβ1 at day 1 and day 7, indicating that TGFβ1 successfully induced tenogenic differentiation of tendon-derived stem cells (TDSCs) (Fig. 1a)

Summary

Introduction

Tendons are a crucial component of the musculoskeletal system and responsible for transmission forces derived from muscle to bone. Tendons are a crucial component of the musculoskeletal system and responsible for the transmission forces derived from muscle to bone. Tendon injury, such as tendon rupture and tendinopathy, is the common disease especially in athletes and the aging population [1, 2]. Endogenous microRNAs (miRNAs) are small noncoding RNA molecules with an average length of ~ 22 nucleotides [6] They negatively regulate the target gene expression by binding the 3′-untranslated region (UTR) of their target mRNA leading to translational repression or mRNA degradation [7]. Thankam et al showed that miR-378a was one of the most highly altered miRNAs in patients

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Conclusion