Summary
Objective
To investigate the role of Piezo1 and Piezo2 in surgically induced osteoarthritis
(OA) in mice.
Design
Male conditional knockout (cKO) mice missing Piezo1 and Piezo2 in the joint using Gdf5-Cre transgenic mice were induced with post-traumatic OA by destabilization of the medial
meniscus (DMM) of the right knee joint at 12 weeks of age. The severity of OA was
histologically assessed at 24 weeks of age. OA-associated pain was evaluated by static
weight bearing analysis. Additionally, articular chondrocytes isolated from cKO mice
were exposed to fluid flow shear stress (FFSS) to evaluate the expression of OA-associated
genes.
Results
Mice with conditional deletion of Piezo1 and Piezo2 showed normal joint development with no overt histological changes in the knee joint
at 12 weeks and 24 weeks. DMM surgery induced moderate to severe OA in both control
and cKO mice (median OARSI score: control, 4.67; cKO, 4.23, P = 0.3082), although a few cKO mice showed milder OA. Pain assessment by static weight-bearing
analysis suggested Piezo ablation in the joint has no beneficial effects on pain.
FFSS increased the expression of OA-related genes both in control and cKO mice to
similar extents.
Conclusion
Piezo1 and Piezo2 are not essential for normal joint development. Genetic ablation
of Piezo channels did not confer evident protective effects on OA progression in mice.
In vitro data suggests that different mechanotransducers other than Piezo channels mediate
FFSS in mechanical stress-induced gene expression.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Osteoarthritis and CartilageAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Mechanotransduction pathways in the regulation of cartilage chondrocyte homoeostasis.J Cell Mol Med. 2020; 24: 5408-5419
- The role of mechanically-activated ion channels Piezo1, Piezo2, and TRPV4 in chondrocyte mechanotransduction and mechano-therapeutics for osteoarthritis.Front Cell Dev Biol. 2022; 10885224
- TRPV4 as a therapeutic target for joint diseases.Naunyn Schmiedebergs Arch Pharmacol. 2015; 388: 437-450
- Cartilage-specific knockout of the mechanosensory ion channel TRPV4 decreases age-related osteoarthritis.Sci Rep. 2016; 629053
- Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues.Bone Res. 2021; 9: 44
- Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.Proc Natl Acad Sci U S A. 2014; 111: E5114-E5122
- The role of matrix metalloproteinases in osteoarthritis pathogenesis: an updated review.Life Sci. 2019; 234116786
- Cytokines and chemokines involved in osteoarthritis pathogenesis.Int J Mol Sci. 2021; : 22
- 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
- BMP receptor signaling is required for postnatal maintenance of articular cartilage.PLoS Biol. 2004; 2: e355
- The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse.Osteoarthritis Cartilage. 2007; 15: 1061-1069
- The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse.Osteoarthritis Cartilage. 2010; 18: S17-S23
- Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways.Genes Dev. 2014; 28: 127-139
- Piezo channels for skeletal development and homeostasis: insights from mouse genetic models.Differentiation. 2022; 126: 10-15
- Urocortin-1 is chondroprotective in response to acute cartilage injury via modulation of Piezo1.Int J Mol Sci. 2022; 23
Article info
Publication history
Published online: February 17, 2023
Accepted:
January 19,
2023
Received:
October 12,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.