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Article

Polycystin-2 Is Required for Chondrocyte Mechanotransduction and Traffics to the Primary Cilium in Response to Mechanical Stimulation

1
Centre for Predictive In Vitro Models, School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK
2
Centre for Endocrinology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
3
Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Elizabeth Bartolak-Suki
Int. J. Mol. Sci. 2021, 22(9), 4313; https://doi.org/10.3390/ijms22094313
Received: 16 March 2021 / Revised: 10 April 2021 / Accepted: 13 April 2021 / Published: 21 April 2021
(This article belongs to the Special Issue Mechanobiology of Organelles)
Primary cilia and associated intraflagellar transport are essential for skeletal development, joint homeostasis, and the response to mechanical stimuli, although the mechanisms remain unclear. Polycystin-2 (PC2) is a member of the transient receptor potential polycystic (TRPP) family of cation channels, and together with Polycystin-1 (PC1), it has been implicated in cilia-mediated mechanotransduction in epithelial cells. The current study investigates the effect of mechanical stimulation on the localization of ciliary polycystins in chondrocytes and tests the hypothesis that they are required in chondrocyte mechanosignaling. Isolated chondrocytes were subjected to mechanical stimulation in the form of uniaxial cyclic tensile strain (CTS) in order to examine the effects on PC2 ciliary localization and matrix gene expression. In the absence of strain, PC2 localizes to the chondrocyte ciliary membrane and neither PC1 nor PC2 are required for ciliogenesis. Cartilage matrix gene expression (Acan, Col2a) is increased in response to 10% CTS. This response is inhibited by siRNA-mediated loss of PC1 or PC2 expression. PC2 ciliary localization requires PC1 and is increased in response to CTS. Increased PC2 cilia trafficking is dependent on the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4) activation. Together, these findings demonstrate for the first time that polycystins are required for chondrocyte mechanotransduction and highlight the mechanosensitive cilia trafficking of PC2 as an important component of cilia-mediated mechanotransduction. View Full-Text
Keywords: Polycystin; Polycystin-1; Polycystin-2; cilia; strain; cartilage; chondrocyte; mechanotransduction Polycystin; Polycystin-1; Polycystin-2; cilia; strain; cartilage; chondrocyte; mechanotransduction
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MDPI and ACS Style

Thompson, C.L.; McFie, M.; Chapple, J.P.; Beales, P.; Knight, M.M. Polycystin-2 Is Required for Chondrocyte Mechanotransduction and Traffics to the Primary Cilium in Response to Mechanical Stimulation. Int. J. Mol. Sci. 2021, 22, 4313. https://doi.org/10.3390/ijms22094313

AMA Style

Thompson CL, McFie M, Chapple JP, Beales P, Knight MM. Polycystin-2 Is Required for Chondrocyte Mechanotransduction and Traffics to the Primary Cilium in Response to Mechanical Stimulation. International Journal of Molecular Sciences. 2021; 22(9):4313. https://doi.org/10.3390/ijms22094313

Chicago/Turabian Style

Thompson, Clare L., Megan McFie, J. P. Chapple, Philip Beales, and Martin M. Knight 2021. "Polycystin-2 Is Required for Chondrocyte Mechanotransduction and Traffics to the Primary Cilium in Response to Mechanical Stimulation" International Journal of Molecular Sciences 22, no. 9: 4313. https://doi.org/10.3390/ijms22094313

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