Suppressed Akt/GSK-3β/β-catenin signaling contributes to excessive adipogenesis of fibro-adipogenic progenitors after rotator cuff tears

• Published in: Cell death discovery Vol. 9; no. 1; p. 312
• Main Authors: Lin, Xingzuan, Wang, Peng, Wang, Wei, Zhou, Hao, Zhu, Siyuan, Feng, Shujing, Chen, Yuzhou, Zhou, Han, Wang, Qichao, Xin, Hanlong, Shao, Xiexiang, Wang, Jianhua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.08.2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/532; 692/699; Achilles tendon; Adipogenesis; AKT protein; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Cycle Analysis; Injuries; Life Sciences; Muscles; Peroxisome proliferator-activated receptors; Rotator cuff; Stem Cells; Wnt protein; β-Catenin
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-023-01618-4

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.