Stretch-Induced Tenomodulin Expression Promotes Tenocyte Migration via F-Actin and Chromatin Remodeling.

Pu Xu,Bingyu Zhang,Bin Deng,Qing Luo,Guanbin Song

doi:10.3390/ijms22094928

Abstract

The mechanosensitive gene tenomodulin (Tnmd) is implicated in tendon maturation and repair. However, the mechanism by which mechanical loading regulates Tnmd’s expression and its role in tenocyte migration is yet to be defined. Here, we show that Tnmd and migration were upregulated in uniaxial cyclic stress-stimulated tenocytes. The knockdown of Tnmd reduced cell migration in the presence and absence of mechanical loading, suggesting that Tnmd is involved in tenocyte migration. Moreover, the treatment of stress-stimulated tenocytes with the actin inhibitor latrunculin (Lat A), histone acetyltransferase inhibitor anacardic acid (ANA), or histone demethylases inhibitor GSK-J4 suppressed Tnmd expression and tenocyte migration. These results show that actin stress fiber formation and chromatin decondensation regulates Tnmd expression, which might then regulate tenocyte migration. Thus, this study proposes the involvement of the actin and chromatin mechanotransduction pathway in the regulation of Tnmd and reveals a novel role of Tnmd in tenocyte migration. The identification of Tnmd function in tenocyte migration provides insight into the molecular mechanisms involved in Tnmd-mediated tendon repair.

Highlights

Tendons are mechanosensitive tissues with a highly organized collagen structure that connect muscle to bone and function as force transmitters during movement [1].tendons withstand tremendous physiological loading, and inappropriate physical training or excessive repetitive stretch can lead to tendon injuries [2]
Tnmd overexpression enhanced tendon-like tissue formation in vivo and positively correlated with tendon healing advancement [9]. These results suggest that maintained Tnmd expression in tendons might be necessary for tenocyte migration during tendon repair
The results showed that tenocytes exposed to stretching of 10% strain, 0.5 Hz, for 1 h had a higher expression of Tnmd at the mRNA (Figure 1C) and protein (Figure 1D,E) levels compared to the unstretched tenocytes

Summary

Introduction

Tendons are mechanosensitive tissues with a highly organized collagen structure that connect muscle to bone and function as force transmitters during movement [1].tendons withstand tremendous physiological loading, and inappropriate physical training or excessive repetitive stretch can lead to tendon injuries [2]. Tnmd overexpression enhanced tendon-like tissue formation in vivo and positively correlated with tendon healing advancement [9]. These results suggest that maintained Tnmd expression in tendons might be necessary for tenocyte migration during tendon repair. Tnmd has been identified as a mechanosensitive gene induced in developing and adult tendons, and its expression in tendons correlates with force intensity [10,11]. Despite the proposed mechanosensitive property of Tnmd and its role in migration, little is known about the mechanisms that induce Tnmd expression in the tendon biomechanical environment

Methods

Results

Conclusion