ArticleInternational journal of molecular sciences2023
Gsmtx4 Alleviated Osteoarthritis through Piezo1/Calcineurin/NFAT1 Signaling Axis under Excessive Mechanical Strain.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 61 citations in OpenAlex.
- Translating mechanobiology in osteoarthritis to biomaterial-informed therapeutic strategies.Mechanobiology in medicine · 2026Review
- Roles of Piezo channels in dentofacial deformity: Onset, orthodontic treatment, and associated diseases.Genes & diseases · 2026Review
- ID3-directed sonogenetics to enhance osteogenesis and bone defect healing.International journal of oral science · 2026Article
- Piezo1-mediated Mechanotransduction in the musculoskeletal system: Signaling networks and therapeutic perspectives.Bone reports · 2026Review
- Review
- Piezo1 channel: structure, mechanogating mechanism, functions, diseases and therapeutic strategy.Molecular biomedicine · 2026Review
- Article
- [Research progress on clinical transformation of Piezo1 in osteoarthritis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- The Interplay of Programmed Cell Death Networks in Cardiovascular Diseases: Mechanisms and Therapeutic Opportunities.Reviews in cardiovascular medicine · 2026Review
- Progress on the mechanism of Piezo1 in mechanical ventilation-induced lung injury.Journal of thoracic disease · 2026Review
- PIEZO1 variants that reduce open channel probability are associated with familial osteoarthritis.The Journal of biological chemistry · 2026Article
- The Role of Piezo 1 in the Study of Intervertebral Disc Degeneration: Phenotype, Mechanism and Treatment.Orthopaedic surgery · 2026Review
- Targeting mechanotransduction components as therapeutic strategies in osteoarthritis.Molecular biology reports · 2026Review
- Electric field stimulation-responsive hydrogels for bone regeneration: from mechanisms to applications.Bone research · 2026Review
- Targeting Piezo1/2 ion channels for modulation of the lymphatic system: mechanisms, applications, and therapeutic prospects.Burns & trauma · 2026Review
- Piezo1-mediated mechanotransduction and metabolic regulation in bone health: molecular mechanisms and implications for bone disorders.Frontiers in cell and developmental biology · 2026Review
- From mechanotransduction to manual therapy: advances in piezo/TRP channels and lumbar degeneration.Frontiers in physiology · 2026Review
- Programmed cell death in degenerative skeletal diseases: molecular crosstalk and combinatorial therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Fibroblasts as key effectors of acupuncture in treatment of rheumatoid arthritis.Frontiers in immunology · 2026Article
- Piezo1 as a mechanical checkpoint in T cell immunotherapy for solid tumors.Frontiers in pharmacology · 2026Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Excessive mechanical strain is the prominent risk factor for osteoarthritis (OA), causing cartilage destruction and degeneration. However, the underlying molecular mechanism contributing to mechanical signaling transduction remains unclear in OA. Piezo type mechanosensitive ion channel component 1 (Piezo1) is a calcium-permeable mechanosensitive ion channel and provides mechanosensitivity to cells, but its role in OA development has not been determined. Herein, we found up-regulated expression of Piezo1 in OA cartilage, and that its activation contributes to chondrocyte apoptosis. The knockdown of Piezo1 could protect chondrocytes from apoptosis and maintain the catabolic and anabolic balance under mechanical strain. In vivo, Gsmtx4, a Piezo1 inhibitor, markedly ameliorated the progression of OA, inhibited the chondrocyte apoptosis, and accelerated the production of the cartilage matrix. Mechanistically, we observed the elevated activity of calcineurin (CaN) and the nuclear transfection of nuclear factor of activated T cells 1 (NFAT1) under mechanical strain in chondrocytes. Inhibitors of CaN or NFAT1 rescued the pathologic changes induced by mechanical strain in chondrocytes. Overall, our findings revealed that Piezo1 was the essential molecule response to mechanical signals and regulated apoptosis and cartilage matrix metabolism via the CaN/NFAT1 signaling axis in chondrocytes, and that Gsmtx4 could be an attractive therapeutic drug for OA treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.