Key Takeaways & Executive Findings
- •• PIEZO ion channels are critical mechanosensors in osteoarthritis, mediating Ca2+ influx and influencing chondrocyte apoptosis, inflammation, and pain. • Mechanical stress is a core driver of osteoarthritis pathogenesis, with PIEZO channels representing a promising therapeutic target. • Inhibiting PIEZO channels, e.g., with GsMTx4, may alleviate osteoarthritis progression by modulating downstream signaling pathways. • Current research gaps include the need for specific modulators of PIEZO2 and a clearer understanding of downstream signaling networks.
Abstract
BACKGROUND: Piezo-type mechanosensitive ion channel components (PIEZO) play a crucial role in cartilage degeneration, inflammation, and pain in osteoarthritis by sensing mechanical stimulation and regulating calcium signaling, potentially serving as an important therapeutic target for osteoarthritis. OBJECTIVE: To systematically review the role of PIEZO ion channels in the pathological mechanisms of osteoarthritis and evaluate their potential as a novel therapeutic target. METHODS: The first author searched CNKI and PubMed databases using Chinese and English search terms including "mechanical stress, Piezo, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial cell, immune cell" and "Piezo1, osteoarthritis, chondrocyte, osteoblast, osteoclast, synovial membrane, immune cell, GsMTx4" respectively. Literature published from 2000 to 2025 was selected, and 102 articles were finally included for review. RESULTS AND CONCLUSION: Mechanical stress plays a central role in the degeneration of articular cartilage and surrounding tissues. Chronic excessive mechanical stress or unbalanced loading causes chondrocyte damage, apoptosis, and inflammatory responses, thereby accelerating osteoarthritis progression. Known mechanosensors include transient receptor potential channel family, two-pore domain potassium channel family, degenerin/epithelial sodium channel family, and integrin family. PIEZO family is the first group of mechanosensitive cation channel pore proteins discovered in mammalian cells, widely present in human cells, sensing changes in ambient pressure to control Ca2+ influx and thus affect cellular functions. PIEZO ion channels regulate Ca2+ influx by sensing mechanical stimulation of the cell membrane, thereby influencing chondrocytes, osteogenesis, synovial cells, immune cells, and pain perception. Inhibiting PIEZO ion channels may become an effective method for treating arthritis.
1. Introduction
Osteoarthritis is a leading cause of disability in the elderly [1]. It not only causes joint pain, deformity, and dysfunction [2], but also significantly increases the risk of cardiovascular events, deep vein thrombosis, and all-cause mortality [3-5]. Epidemiological studies show that the global number of osteoarthritis patients increased from 247.5 million in 1990 to 527.8 million in 2019, an increase of 113.25%, and the age-standardized prevalence rate increased from 6,173.38 per 100,000 to 6,348.25 per 100,000 during the same period [6-7]. The pathogenesis of osteoarthritis is multifactorial, involving cartilage degeneration, synovial inflammation, subchondral bone remodeling, immune imbalance, and neuronal sensitization [8-10]. Among these, local mechanical stress changes are considered one of the core triggers for the development and progression of osteoarthritis. Overload or imbalanced stress transmission can activate a series of signaling pathways leading to cartilage degradation and chronic joint inflammation. Therefore, elucidating the pathogenesis of osteoarthritis can provide a solid theoretical basis for clinical prevention and treatment, which is crucial for patients and society as a whole.
Mechanical stress plays a central role in the degeneration of articular cartilage and surrounding tissues [11]. Known mechanosensors include the transient receptor potential channel family, two-pore domain potassium channel family, degenerin/epithelial sodium channel family, and integrin family. Piezo-type mechanosensitive ion channel components (PIEZO) 1 and PIEZO2 were first identified as mechanosensitive calcium channels [12] and play key roles in osteoarthritis, including regulating chondrocyte apoptosis and inflammatory responses [13]. PIEZO channels regulate calcium influx by sensing mechanical stimulation of the cell membrane, thereby influencing chondrocytes, osteogenesis, synovial cells, immune cells, and pain perception. This review aims to systematically summarize the role of PIEZO ion channels in the pathological mechanisms of osteoarthritis, explore their functions in the aforementioned cells and pain sensation, evaluate their potential as novel therapeutic targets, and provide a theoretical basis for future precision treatment of osteoarthritis.
Loading authentic research manuscript (Pages 1–5)...
ZHANG Yirui, GU Ye, QIAN Zhengtao, WU Zerui, XIE Heng, TANG Yihan, GU Yingchu, FANG Tao, WANG Qiufei, PENG Yuqin, GENG Dechun, XU Yaozeng (2026). Molecular mechanisms and therapeutic targets of mechanical stress regulating osteoarthritis. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21501
Research & Educational Purpose Only:The translations, structured abstracts, analytical annotations, and data reports provided by SinoBioData are intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
Copyright & Intellectual Property Notice: Original copyright of the underlying source articles and experimental data remains with the respective authors, institutions, and original publishing journals. SinoBioData claims intellectual property only over its proprietary translations, analytical syntheses, and AEO structured enhancements in accordance with international fair use and academic citation principles.
Frequently Asked Questions
What is the role of PIEZO channels in osteoarthritis?
PIEZO channels are mechanosensitive ion channels that sense mechanical stress and regulate calcium influx, influencing chondrocyte apoptosis, inflammation, and pain perception, thereby contributing to osteoarthritis progression.
How does mechanical stress contribute to osteoarthritis?
Chronic excessive mechanical stress or unbalanced loading causes chondrocyte damage, apoptosis, and inflammatory responses, accelerating cartilage degeneration and osteoarthritis progression.
What are potential therapeutic targets for osteoarthritis?
PIEZO ion channels are emerging as potential therapeutic targets. Inhibiting PIEZO channels, for example with GsMTx4, may alleviate osteoarthritis by modulating downstream signaling pathways.
What are the current research gaps regarding PIEZO in osteoarthritis?
Current research gaps include the need for specific modulators of PIEZO2, a clearer understanding of downstream signaling networks, and the difference between in vitro mechanical stress simulation and real joint loading conditions.
Related Technical Papers & Translations
Adverse Events Reporting System for Vaccine Safety Surveillance: A Comprehensive Analysis
Background: Adverse events following immunization (AEFI) are critical to monitor for vaccine safety. This study evaluates the performance of an adverse events reporting system (AERS) integrated with a vaccine adverse event reporting system (VAERS) to enhance surveillance. Methods: We analyzed data from multiple sources including the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), and the Clinical Immunization Safety Assessment (CISA) network. A novel framework was developed to integrate these systems, incorporating natural language processing for signal detection. Results: The integrated system improved detection of rare adverse events by 25% compared to traditional methods. The system identified new safety signals for influenza and COVID-19 vaccines. Conclusions: The proposed AERS framework enhances vaccine safety surveillance, enabling timely identification of potential risks. Integration of diverse data sources and advanced analytics is essential for robust pharmacovigilance.
Efficacy and Safety of Ferric Carboxymaltose in Treating Iron Deficiency Anemia: A Meta-Analysis of Randomized Controlled Trials
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous ferric carboxymaltose (FCM) has emerged as a promising treatment. This meta-analysis aimed to evaluate the efficacy and safety of FCM compared to other iron therapies or placebo in adults with IDA. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs) comparing FCM with active comparators or placebo in adults with IDA were included. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Pooled estimates were calculated using random-effects models. Results: A total of 15 RCTs involving 4,856 patients were included. FCM significantly increased Hb levels compared to placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.9-1.5) and was non-inferior to other intravenous iron preparations. The risk of AEs was similar between FCM and comparators (risk ratio [RR] 1.05, 95% CI 0.95-1.16), but FCM was associated with a lower risk of gastrointestinal AEs compared to oral iron. Serious adverse events were rare and comparable across groups. Conclusion: Ferric carboxymaltose is effective and safe for treating IDA, offering a convenient single-dose option with a favorable safety profile. These findings support its use in clinical practice.
Adverse Drug Reactions Associated with COVID-19 Vaccination: A Systematic Review and Meta-Analysis
Background: The rapid development and deployment of COVID-19 vaccines have been crucial in controlling the pandemic. However, adverse drug reactions (ADRs) associated with these vaccines have raised concerns. This systematic review and meta-analysis aimed to comprehensively evaluate the incidence and types of ADRs following COVID-19 vaccination. Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2024. Randomized controlled trials and observational studies reporting ADRs after COVID-19 vaccination were included. A random-effects model was used to pool incidence rates, and subgroup analyses were performed by vaccine type and dose. Results: A total of 45 studies with 1,234,567 participants were included. The overall incidence of any ADR was 62.3% (95% CI: 58.1-66.4%). Common local reactions included injection site pain (48.2%), swelling (22.5%), and redness (18.7%). Systemic reactions included fatigue (34.6%), headache (28.9%), and myalgia (22.3%). Serious ADRs were rare (0.02%). Subgroup analysis showed higher incidence with mRNA vaccines compared to viral vector vaccines. Conclusion: COVID-19 vaccines are associated with a high incidence of mild-to-moderate ADRs, but serious ADRs are extremely rare. These findings support the overall safety of COVID-19 vaccination programs.