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[Research progress on clinical transformation of Piezo1 in osteoarthritis]
Yiyang Wang1, Ning Wei1, Zhanle Zheng1
1Knee Joint Preservation Center, Hebei Medical University Third Hospital, Shijiazhuang Hebei, 050051, P. R. China.
Objective:
To review the role of the mechanosensitive ion channel Piezo1 in osteoarthritis (OA) pathogenesis and summarize recent advances in its clinical transformation as a potential therapeutic target.
Methods:
The recent domestic and international research literature was reviewed. Recent studies on Piezo1 in chondrocyte injury, inflammation, extracellular matrix degradation, and osteophyte formation were analyzed, along with Piezo1-targeted inhibitors, activators, and modulators.
Results:
Piezo1 senses abnormal mechanical stress and mediates Ca 2+ influx, activating PI3K/AKT/mTOR and MAPK/ERK signaling pathways, thereby promoting chondrocyte apoptosis, impaired autophagy, and matrix degradation. Preclinical studies suggest that GsMTx4, Piezo1-siRNA, Dooku1, and artemisinin may confer chondroprotective effects, but their specificity, stability, delivery efficiency, and safety require further verification.
Conclusion:
Piezo1 is a critical link between mechanical stress and OA progression, representing a potential therapeutic target. Future research should focus on elucidating mechanisms, developing highly specific modulators and targeted delivery systems, and conducting rigorous preclinical and clinical studies to promote clinical transformation.
Insights
The mechanosensitive ion channel Piezo1 plays a key role in osteoarthritis (OA) pathogenesis by sensing mechanical stress. Targeting Piezo1 offers a promising therapeutic strategy for OA treatment.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Rheumatology
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and pain.
- Mechanical stress is a known contributor to OA pathogenesis.
- The role of mechanosensitive ion channels in OA is an emerging area of research.
Purpose of the Study:
- To review the role of the mechanosensitive ion channel Piezo1 in osteoarthritis (OA) pathogenesis.
- To summarize recent advances in Piezo1 as a potential therapeutic target for OA.
Main Methods:
- A comprehensive review of recent domestic and international research literature on Piezo1.
- Analysis of studies investigating Piezo1's involvement in chondrocyte injury, inflammation, extracellular matrix degradation, and osteophyte formation.
- Examination of Piezo1-targeted inhibitors, activators, and modulators.
Main Results:
- Piezo1 mediates calcium (Ca2+) influx in response to abnormal mechanical stress, activating PI3K/AKT/mTOR and MAPK/ERK signaling pathways.
- Activation of these pathways promotes chondrocyte apoptosis, impairs autophagy, and leads to matrix degradation.
- Preclinical studies indicate potential chondroprotective effects of GsMTx4, Piezo1-siRNA, Dooku1, and artemisinin, though further verification is needed.
Conclusions:
- Piezo1 is a critical mediator linking mechanical stress to OA progression.
- Piezo1 represents a promising therapeutic target for OA.
- Future research should focus on mechanism elucidation, developing specific modulators, and conducting rigorous clinical studies.
