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Destabilization of the Medial Meniscus and Cartilage Scratch Murine Model of Accelerated Osteoarthritis
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High-intensity running exercise promotes knee meniscal damage via the PI3K/AKT/mTOR axis
Juncheng Yao1,2, Haolin Ke1,2,3,4, Guangxin Huang1,2
1Department of Sports Medicine, Center for Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Bone & Joint Research
|November 7, 2025
Summary
Excessive mechanical stress triggers meniscal degeneration by activating the PI3K/AKT/mTOR pathway. Inhibiting this pathway with rapamycin successfully mitigated damage in mouse and human meniscal cells, offering a potential osteoarthritis intervention.
Area of Science:
- Orthopedics
- Cellular Biology
- Molecular Medicine
Background:
- Meniscal degeneration is a key factor in osteoarthritis development.
- Understanding the molecular mechanisms of meniscal damage is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the cellular and molecular pathways involved in meniscal degeneration.
- To identify potential therapeutic targets for osteoarthritis interventions.
Main Methods:
- A mouse model of meniscal injury was created using a running platform.
- Human meniscal cells and tissues were subjected to mechanical stress.
- Western blot, qRT-PCR, and transcriptome sequencing were employed to analyze molecular responses.
- Rapamycin was tested for its therapeutic effects on meniscal damage.
Main Results:
- High-intensity running led to progressive meniscal degeneration in mice.
- Mechanical stress activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in meniscal cells.
- Rapamycin treatment significantly reduced meniscal degeneration in both mouse models and human cells.
Conclusions:
- Prolonged mechanical stress contributes to meniscal degeneration via the PI3K/AKT/mTOR axis.
- Inhibition of the PI3K/AKT/mTOR pathway presents a promising therapeutic strategy for osteoarthritis.
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