The Emerging Role of Piezo1 in the Musculoskeletal System and Disease

Overview

Journal Theranostics

Date 2024 Jul 12

PMID 38994033

Authors

Lei Lei

Zhenkang Wen

Mingde Cao

Haozhi Zhang

Samuel Ka-Kin Ling

Bruma Sai-Chuen Fu

Ling Qin

Jiankun Xu

Patrick Shu-Hang Yung

Affiliations

Soon will be listed here.

Abstract

Piezo1, a mechanosensitive ion channel, has emerged as a key player in translating mechanical stimuli into biological signaling. Its involvement extends beyond physiological and pathological processes such as lymphatic vessel development, axon growth, vascular development, immunoregulation, and blood pressure regulation. The musculoskeletal system, responsible for structural support, movement, and homeostasis, has recently attracted attention regarding the significance of Piezo1. This review aims to provide a comprehensive summary of the current research on Piezo1 in the musculoskeletal system, highlighting its impact on bone formation, myogenesis, chondrogenesis, intervertebral disc homeostasis, tendon matrix cross-linking, and physical activity. Additionally, we explore the potential of targeting Piezo1 as a therapeutic approach for musculoskeletal disorders, including osteoporosis, muscle atrophy, intervertebral disc degeneration, and osteoarthritis.

Citing Articles

Tensile force promotes osteogenic differentiation via ephrinB2-EphB4 signaling pathway in orthodontic tooth movement.

Yu H, Wei X, Jiang H, Qi H, Zhang Y, Hu M BMC Oral Health. 2025; 25(1):118.

PMID: 39844202 PMC: 11755856. DOI: 10.1186/s12903-025-05491-8.

References

Xu X, Liu S, Liu H, Ru K, Jia Y, Wu Z . Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone. Int J Mol Sci. 2021; 22(12). PMC: 8234635. DOI: 10.3390/ijms22126429. View

Sun Y, Leng P, Li D, Gao H, Li Z, Li C . Mechanism of Abnormal Chondrocyte Proliferation Induced by Piezo1-siRNA Exposed to Mechanical Stretch. Biomed Res Int. 2020; 2020:8538463. PMC: 7661139. DOI: 10.1155/2020/8538463. View

Ge J, Li W, Zhao Q, Li N, Chen M, Zhi P . Architecture of the mammalian mechanosensitive Piezo1 channel. Nature. 2015; 527(7576):64-9. DOI: 10.1038/nature15247. View

Passini F, Jaeger P, Saab A, Hanlon S, Chittim N, Arlt M . Shear-stress sensing by PIEZO1 regulates tendon stiffness in rodents and influences jumping performance in humans. Nat Biomed Eng. 2021; 5(12):1457-1471. PMC: 7612848. DOI: 10.1038/s41551-021-00716-x. View

Xing Y, Yang B, He Y, Xie B, Zhao T, Chen J . Effects of mechanosensitive ion channel Piezo1 on proliferation and osteogenic differentiation of human dental follicle cells. Ann Anat. 2021; 239:151847. DOI: 10.1016/j.aanat.2021.151847. View

Snedeker J, Foolen J . Tendon injury and repair - A perspective on the basic mechanisms of tendon disease and future clinical therapy. Acta Biomater. 2017; 63:18-36. DOI: 10.1016/j.actbio.2017.08.032. View

Ma N, Chen D, Lee J, Kuri P, Hernandez E, Kocan J . Piezo1 regulates the regenerative capacity of skeletal muscles via orchestration of stem cell morphological states. Sci Adv. 2022; 8(11):eabn0485. PMC: 8932657. DOI: 10.1126/sciadv.abn0485. View

Marouli E, Graff M, Medina-Gomez C, Lo K, Wood A, Kjaer T . Rare and low-frequency coding variants alter human adult height. Nature. 2017; 542(7640):186-190. PMC: 5302847. DOI: 10.1038/nature21039. View

Ridone P, Vassalli M, Martinac B . Piezo1 mechanosensitive channels: what are they and why are they important. Biophys Rev. 2019; 11(5):795-805. PMC: 6815293. DOI: 10.1007/s12551-019-00584-5. View

10.

Wang H, Yuan Z, Wang B, Li B, Lv H, He J . COMP (Cartilage Oligomeric Matrix Protein), a Novel PIEZO1 Regulator That Controls Blood Pressure. Hypertension. 2022; 79(3):549-561. DOI: 10.1161/HYPERTENSIONAHA.121.17972. View

11.

Glyn-Jones S, Palmer A, Agricola R, Price A, Vincent T, Weinans H . Osteoarthritis. Lancet. 2015; 386(9991):376-87. DOI: 10.1016/S0140-6736(14)60802-3. View

12.

Huang H, Bae C, Sachs F, Suchyna T . Caveolae regulation of mechanosensitive channel function in myotubes. PLoS One. 2013; 8(8):e72894. PMC: 3758351. DOI: 10.1371/journal.pone.0072894. View

13.

Chen Y, Braun B, Menger M, Ronniger M, Falldorf K, Histing T . Intermittent Exposure to a 16 Hz Extremely Low Frequency Pulsed Electromagnetic Field Promotes Osteogenesis In Vitro through Activating Piezo 1-Induced Ca Influx in Osteoprogenitor Cells. J Funct Biomater. 2023; 14(3). PMC: 10055851. DOI: 10.3390/jfb14030165. View

14.

Yoneda M, Suzuki H, Hatano N, Nakano S, Muraki Y, Miyazawa K . PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation. Int J Mol Sci. 2019; 20(19). PMC: 6801562. DOI: 10.3390/ijms20194960. View

15.

Peyronnet R, Martins J, Duprat F, Demolombe S, Arhatte M, Jodar M . Piezo1-dependent stretch-activated channels are inhibited by Polycystin-2 in renal tubular epithelial cells. EMBO Rep. 2013; 14(12):1143-8. PMC: 3981085. DOI: 10.1038/embor.2013.170. View

16.

Zhou W, Shi Y, Wang H, Chen L, Yu C, Zhang X . Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy. Exp Mol Med. 2022; 54(7):1038-1048. PMC: 9355987. DOI: 10.1038/s12276-022-00811-2. View

17.

Liedert A, Kaspar D, Blakytny R, Claes L, Ignatius A . Signal transduction pathways involved in mechanotransduction in bone cells. Biochem Biophys Res Commun. 2006; 349(1):1-5. DOI: 10.1016/j.bbrc.2006.07.214. View

18.

Peng Y, Du J, Gunther S, Guo X, Wang S, Schneider A . Mechano-signaling via Piezo1 prevents activation and p53-mediated senescence of muscle stem cells. Redox Biol. 2022; 52:102309. PMC: 9005960. DOI: 10.1016/j.redox.2022.102309. View

19.

Rubin C . Skeletal strain and the functional significance of bone architecture. Calcif Tissue Int. 1984; 36 Suppl 1:S11-8. DOI: 10.1007/BF02406128. View

20.

Lee W, Leddy H, Chen Y, Lee S, Zelenski N, McNulty A . Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc Natl Acad Sci U S A. 2014; 111(47):E5114-22. PMC: 4250098. DOI: 10.1073/pnas.1414298111. View