Polycystin-2 Is Required for Chondrocyte Mechanotransduction and Traffics to the Primary Cilium in Response to Mechanical Stimulation
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作者:
Thompson, Clare L.
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Queen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, EnglandQueen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, England
Thompson, Clare L.
[1
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McFie, Megan
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Queen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, EnglandQueen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, England
McFie, Megan
[1
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Chapple, J. Paul
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Queen Mary Univ London, Sch Med & Dent, William Harvey Res Inst, Ctr Endocrinol, London EC1M 6BQ, EnglandQueen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, England
Chapple, J. Paul
[2
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Beales, Philip
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UCL Great Ormond St Inst Child Hlth, Genet & Genom Med, London WC1N 1EH, EnglandQueen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, England
Beales, Philip
[3
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Knight, Martin M.
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Queen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, EnglandQueen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, England
Knight, Martin M.
[1
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机构:
[1] Queen Mary Univ London, Sch Engn & Mat Sci, Ctr Predict Vitro Models, London E1 4NS, England
[2] Queen Mary Univ London, Sch Med & Dent, William Harvey Res Inst, Ctr Endocrinol, London EC1M 6BQ, England
[3] UCL Great Ormond St Inst Child Hlth, Genet & Genom Med, London WC1N 1EH, England
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.
机构:
Univ Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, ScotlandUniv Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, Scotland
Zhou, Y
Robinson, H
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Univ Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, ScotlandUniv Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, Scotland
Robinson, H
Millward-Sadler, J
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Univ Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, ScotlandUniv Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, Scotland
Millward-Sadler, J
Goldring, M
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Univ Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, ScotlandUniv Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, Scotland
Goldring, M
Nuki, G
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Univ Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, ScotlandUniv Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Dept Med Sci, Edinburgh EH4 2XU, Midlothian, Scotland
机构:
KIST, Ctr Funct Connect, Seoul 136791, South Korea
KIST, Ctr Neural Sci, Seoul 136791, South KoreaKIST, Ctr Funct Connect, Seoul 136791, South Korea
Lee, Jaekwang
Chun, Ye-Eun
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KIST, Ctr Funct Connect, Seoul 136791, South Korea
KIST, Ctr Neural Sci, Seoul 136791, South Korea
UST, Neurosci Program, Daejeon 305350, South KoreaKIST, Ctr Funct Connect, Seoul 136791, South Korea
Chun, Ye-Eun
Han, Kyung-Seok
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KIST, Ctr Funct Connect, Seoul 136791, South Korea
KIST, Ctr Neural Sci, Seoul 136791, South KoreaKIST, Ctr Funct Connect, Seoul 136791, South Korea
Han, Kyung-Seok
Lee, Jungmoo
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KIST, Ctr Funct Connect, Seoul 136791, South Korea
KIST, Ctr Neural Sci, Seoul 136791, South Korea
KU KIST, Grad Sch Converging Sci & Technol, Seoul 136701, South KoreaKIST, Ctr Funct Connect, Seoul 136791, South Korea
Lee, Jungmoo
Woo, Dong Ho
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机构:
KIST, Ctr Funct Connect, Seoul 136791, South Korea
KIST, Ctr Neural Sci, Seoul 136791, South KoreaKIST, Ctr Funct Connect, Seoul 136791, South Korea
Woo, Dong Ho
Lee, C. Justin
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KIST, Ctr Funct Connect, Seoul 136791, South Korea
KIST, Ctr Neural Sci, Seoul 136791, South Korea
UST, Neurosci Program, Daejeon 305350, South Korea
KU KIST, Grad Sch Converging Sci & Technol, Seoul 136701, South KoreaKIST, Ctr Funct Connect, Seoul 136791, South Korea
机构:
St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
Ryerson Univ, Dept Chem Engn, Kerr Hall South, Toronto, ON KHS 241N, CanadaSt Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
Soave, Arianna
Chiu, Loraine L. Y.
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St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
Ryerson Univ, Dept Chem Engn, Kerr Hall South, Toronto, ON KHS 241N, CanadaSt Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
Chiu, Loraine L. Y.
Momin, Aisha
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St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
Ryerson Univ, Dept Chem Engn, Kerr Hall South, Toronto, ON KHS 241N, CanadaSt Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
Momin, Aisha
Waldman, Stephen D.
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St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada
Ryerson Univ, Dept Chem Engn, Kerr Hall South, Toronto, ON KHS 241N, Canada
Ryerson Univ, Fac Engn & Architectural Sci, Toronto, ON M5B 2K3, CanadaSt Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada