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

Cell Death Discovery

Article

Wei Wang¹  Shujing Feng²  Hanlong Xin³  Siyuan Zhu⁴  Yuzhou Chen⁴  Xiexiang Shao⁴  Qichao Wang⁴  Xingzuan Lin⁴  Jianhua Wang⁴  Peng Wang⁴  Hao Zhou⁴  Han Zhou⁴ 

[1] Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China;Shanghai University of Sport, Shanghai, China;Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China;Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;

关键词: ;   

DOI  :  10.1038/s41420-023-01618-4

 received in 2023-04-18, accepted in 2023-08-17,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Cell Death Differentiation Association (ADMC) 2023

【 图 表 】

Fig. 3

Fig. 5

Fig. 4

Fig. 5

Fig. 6

Fig. 1

Fig. 1

13570_2023_282_Article_IEq5.gif