Suppressed Akt/GSK-3β/β-catenin Signaling Contributes to Excessive Adipogenesis of Fibro-adipogenic Progenitors After Rotator Cuff Tears

Overview

Journal Cell Death Discov

Date 2023 Aug 25

PMID 37626040

Authors

Xingzuan Lin

Peng Wang

Wei Wang

Hao Zhou

Siyuan Zhu

Shujing Feng

Yuzhou Chen

Han Zhou

Qichao Wang

Hanlong Xin

Xiexiang Shao

Jianhua Wang

Affiliations

Soon will be listed here.

Abstract

Muscular fatty infiltration is a common and troublesome pathology after rotator cuff tears (RCT), which mainly derives from fibro-adipogenic progenitors (FAPs). Compared to the RCT, fatty infiltration is not so severe in Achilles tendon tears (ATT). The knowledge of why fatty infiltration is more likely to occur after RCT is limited. In this study, more severe fatty infiltration was verified in supraspinatus than gastrocnemius muscles after tendon injury. Additionally, we revealed higher adipogenic differentiation ability of RCT-FAPs in vitro. Activation of Akt significantly stimulated GSK-3β/β-catenin signaling and thus decreased PPARγ expression and adipogenesis of RCT-FAPs, while the inhibition effect was attenuated by β-catenin inhibitor. Furthermore, Wnt signaling activator BML-284 limited adipogenesis of RCT-FAPs, alleviated muscular fatty infiltration, and improved parameters in gait analysis and treadmill test for RCT model. In conclusion, our study demonstrated that suppressed Akt/GSK-3β/β-catenin signaling increased PPARγ expression and thus contributed to excessive adipogenesis in RCT-FAPs. Modulation of Akt/GSK-3β/β-catenin signaling ameliorated excessive fatty infiltration of rotator cuff muscles and improved shoulder function after RCT.

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