Role of Piezo mechanosensitive ion channels in the osteoarticular system_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHEN Guohui ^1,2 , LI Yaxing ^1,2 ,  ZHANG Hui ^1,2 ,  XIE Huiqi ^2,3

1. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;
2. Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;
3. Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding author：

ZHANG Hui, Email: footanklecenterwch@163.com; XIE Huiqi, Email: xiehuiqi@scu.edu.cn

Keywords：

Osteoarticular system; Piezo; mechanosensitive ion channel; mechanical transduction

DOI：

10.7507/1002-1892.202310092

Video：

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Objective To summarize the role of Piezo mechanosensitive ion channels in the osteoarticular system, in order to provide reference for subsequent research. Methods Extensive literature review was conducted to summarize the structural characteristics, gating mechanisms, activators and blockers of Piezo ion channels, as well as their roles in the osteoarticular systems. Results The osteoarticular system is the main load-bearing and motor tissue of the body, and its ability to perceive and respond to mechanical stimuli is one of the guarantees for maintaining normal physiological functions of bones and joints. The occurrence and development of many osteoarticular diseases are closely related to abnormal mechanical loads. At present, research shows that Piezo mechanosensitive ion channels differentiate towards osteogenesis by responding to stretching stimuli and regulating cellular Ca²⁺ influx signals; and it affects the proliferation and migration of osteoblasts, maintaining bone homeostasis through cellular communication between osteoblasts-osteoclasts. Meanwhile, Piezo1 protein can indirectly participate in regulating the formation and activity of osteoclasts through its host cells, thereby regulating the process of bone remodeling. During mechanical stimulation, the Piezo1 ion channel maintains bone homeostasis by regulating the expressions of Akt and Wnt1 signaling pathways. The sensitivity of Piezo1/2 ion channels to high strain mechanical signals, as well as the increased sensitivity of Piezo1 ion channels to mechanical transduction mediated by Ca²⁺ influx and inflammatory signals in chondrocytes, is expected to become a new entry point for targeted prevention and treatment of osteoarthritis. But the specific way mechanical stimuli regulate the physiological/pathological processes of bones and joints still needs to be clarified. Conclusion Piezo mechanosensitive ion channels give the osteoarticular system with important abilities to perceive and respond to mechanical stress, playing a crucial mechanical sensing role in its cellular fate, bone development, and maintenance of bone and cartilage homeostasis.

Citation： CHEN Guohui, LI Yaxing, ZHANG Hui, XIE Huiqi. Role of Piezo mechanosensitive ion channels in the osteoarticular system. Chinese Journal of Reparative and Reconstructive Surgery, 2024, 38(2): 240-248. doi: 10.7507/1002-1892.202310092 Copy

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1. Murthy SE, Dubin AE, Patapoutian A. Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat Rev Mol Cell Biol, 2017, 18(12): 771-783.
2. Klein-Nulend J, Bacabac RG, Veldhuijzen JP, et al. Microgravity and bone cell mechanosensitivity. Adv Space Res, 2003, 32(8): 1551-1559.
3. Romani P, Valcarcel-Jimenez L, Frezza C, et al. Crosstalk between mechanotransduction and metabolism. Nat Rev Mol Cell Biol, 2021, 22(1): 22-38.
4. Ostrow LW, Sachs F. Mechanosensation and endothelin in astrocytes—hypothetical roles in CNS pathophysiology. Brain Res Brain Res Rev, 2005, 48(3): 488-508.
5. Duscher D, Maan ZN, Wong VW, et al. Mechanotransduction and fibrosis. J Biomech, 2014, 47(9): 1997-2005.
6. Lyon RC, Zanella F, Omens JH, et al. Mechanotransduction in cardiac hypertrophy and failure. Circ Res, 2015, 116(8): 1462-1476.
7. Broders-Bondon F, Nguyen Ho-Bouldoires TH, Fernandez-Sanchez ME, et al. Mechanotransduction in tumor progression: The dark side of the force. J Cell Biol, 2018, 217(5): 1571-1587.
8. Vollrath MA, Kwan KY, Corey DP. The micromachinery of mechanotransduction in hair cells. Annu Rev Neurosci, 2007, 30: 339-365.
9. Qin L, He T, Chen S, et al. Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues. Bone Res, 2021, 9(1): 44.
10. Herrmann M, Engelke K, Ebert R, et al. Interactions between muscle and bone-where physics meets biology. Biomolecules, 2020, 10(3): 432.
11. Scott A, Khan KM, Duronio V, et al. Mechanotransduction in human bone: in vitro cellular physiology that underpins bone changes with exercise. Sports Med, 2008, 38(2): 139-160.
12. Xu X, Liu S, Liu H, et al. Piezo channels: awesome mechanosensitive structures in cellular mechanotransduction and their role in bone. Int J Mol Sci, 2021, 22(12): 6429.
13. Wolff J. The law of bone remodelling. Berlin: Springer-Verlag, 1986: 3-21.
14. Wolff J. Das gesetz der transformation der knochen. Deutsche Medizinische Wochenschrift, 1893, 19: 1222-1224.
15. Pearson OM, Lieberman DE. The aging of Wolff’s “law”: ontogeny and responses to mechanical loading in cortical bone. Am J Phys Anthropol, 2004, Suppl 39: 63-99.
16. Lee TC, Taylor D. Bone remodelling: should we cry Wolff? Ir J Med Sci, 1999, 168(2): 102-105.
17. Mullender MG, Huiskes R. Proposal for the regulatory mechanism of Wolff's law. J Orthop Res, 1995, 13(4): 503-512.
18. Barak MM, Lieberman DE, Hublin JJ. A Wolff in sheep’s clothing: trabecular bone adaptation in response to changes in joint loading orientation. Bone, 2011, 49(6): 1141-1151.
19. Johnson KA. Wolff’s law continues to inspire orthopaedic research. Vet Comp Orthop Traumatol, 2014, 27(1): Ⅴ-Ⅵ.
20. Ilizarov GA. Clinical application of the tension-stress effect for limb lengthening. Clin Orthop Relat Res, 1990, (250): 8-26.
21. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues: Part Ⅱ. The influence of the rate and frequency of distraction. Clin Orthop Relat Res, 1989, (239): 263-285.
22. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues. Part Ⅰ. The influence of stability of fixation and soft-tissue preservation. Clin Orthop Relat Res, 1989, (238): 249-281.
23. Xu BY, Jin Y, Ma XH, et al. The potential role of mechanically sensitive ion channels in the physiology, injury, and repair of articular cartilage. J Orthop Surg (Hong Kong), 2020, 28(3): 2309499020950262.
24. Lee W, Nims RJ, Savadipour A, et al. Inflammatory signaling sensitizes Piezo1 mechanotransduction in articular chondrocytes as a pathogenic feed-forward mechanism in osteoarthritis. Proc Natl Acad Sci U S A, 2021, 118(13): e2001611118.
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Chinese Journal of Reparative and Reconstructive Surgery

Role of Piezo mechanosensitive ion channels in the osteoarticular system

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