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The Glycogen Synthase Kinase-3 Inhibitor CHIR99021 Reduces Fatty Infiltration and Muscle Atrophy After Rotator Cuff
Pu Zhang1, Meng Zhou2,3, Yiming Zhu2
1Fourth School of Clinical Medicine, Peking University, Beijing, China.
The American Journal of Sports Medicine
|February 24, 2025
Summary
A new study shows that inhibiting GSK-3 with CHIR99021 can reduce fatty infiltration and muscle atrophy in rotator cuff tears (RCTs). This finding offers a potential new treatment for RCTs, improving clinical outcomes.
Area of Science:
- Orthopedics
- Regenerative Medicine
- Molecular Biology
Background:
- Rotator cuff tears (RCTs) lead to muscle atrophy and fatty infiltration, impairing clinical outcomes.
- Current therapies for inhibiting fatty infiltration in RCTs are limited.
Purpose of the Study:
- Identify pathways linked to fatty infiltration in RCTs using RNA sequencing.
- Evaluate the therapeutic potential of the GSK-3 inhibitor CHIR99021 for RCTs.
Main Methods:
- RNA sequencing of supraspinatus muscle biopsies from RCT patients.
- In vitro studies using fibro-adipogenic progenitors (FAPs) and C2C12 myoblasts treated with CHIR99021.
- In vivo studies using a mouse model of RCT treated with CHIR99021.
Main Results:
- RNA sequencing revealed Akt/GSK-3 pathway upregulation in RCT samples and FAPs.
- CHIR99021 inhibited adipogenesis in FAPs and promoted myogenesis in C2C12 cells.
- In mice, CHIR99021 reduced fatty infiltration and muscle atrophy, promoting myogenesis.
Conclusions:
- The Akt/GSK-3 pathway is a potential therapeutic target for RCTs.
- CHIR99021 effectively alleviates fatty infiltration and muscle atrophy in vitro and in vivo.
- GSK-3 inhibition presents a promising therapeutic strategy for rotator cuff tear degeneration.
