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

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

  • Cell Death Discov. 2023 Aug 25;9(1):312. doi: 10.1038/s41420-023-01618-4.
Xingzuan Lin # 1 Peng Wang # 1 Wei Wang # 2 Hao Zhou 1 Siyuan Zhu 1 Shujing Feng 3 Yuzhou Chen 1 Han Zhou 1 Qichao Wang 1 Hanlong Xin 4 Xiexiang Shao 5 Jianhua Wang 6
Affiliations

Affiliations

  • 1 Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China.
  • 3 Shanghai University of Sport, Shanghai, China.
  • 4 Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China. 8903@enzemed.com.
  • 5 Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. shaoxiexiang@hotmail.com.
  • 6 Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. shwangjianhua@gmail.com.
  • # Contributed equally.
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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