Shear-stress sensing by PIEZO1 regulates tendon stiffness in rodents and influences jumping performance in humans

被引:91
作者
Passini, Fabian S. [1 ,2 ]
Jaeger, Patrick K. [1 ,2 ]
Saab, Aiman S. [3 ,4 ,5 ]
Hanlon, Shawn [6 ]
Chittim, Nicole A. [1 ,2 ]
Arlt, Matthias J. [1 ,2 ]
Ferrari, Kim David [3 ,4 ,5 ]
Haenni, Dominik [7 ]
Caprara, Sebastiano [1 ,2 ]
Bollhalder, Maja [1 ,2 ]
Niederoest, Barbara [1 ,2 ]
Horvath, Aron N. [1 ,2 ]
Goetschi, Tobias [1 ,2 ]
Ma, Shang [8 ]
Passini-Tall, Bettina [1 ]
Fucentese, Sandro F. [1 ]
Blache, Ulrich [1 ,2 ]
Silvan, Unai [1 ,2 ]
Weber, Bruno [3 ,4 ,5 ]
Silbernagel, Karin Graevare [6 ]
Snedeker, Jess G. [1 ,2 ]
机构
[1] Univ Zurich, Univ Hosp Balgrist, Zurich, Switzerland
[2] Swiss Fed Inst Technol, Inst Biomech, Zurich, Switzerland
[3] Univ Zurich, Inst Pharmacol & Toxicol, Zurich, Switzerland
[4] Univ Zurich, Neurosci Ctr, Zurich, Switzerland
[5] Swiss Fed Inst Technol, Zurich, Switzerland
[6] Univ Delaware, Dept Phys Therapy, Newark, DE USA
[7] Univ Zurich, Ctr Microscopy & Image Anal, Zurich, Switzerland
[8] Scripps Res, Dorris Neurosci Ctr, Dept Neurosci, Howard Hughes Med Inst, La Jolla, CA USA
基金
瑞士国家科学基金会;
关键词
ACHILLES-TENDON; MECHANICAL-PROPERTIES; COLLAGEN; CHANNEL; TENDINOPATHY; GLYCATION; STRETCH; PORE; FLOW; PRESSURE;
D O I
10.1038/s41551-021-00716-x
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Athletic performance relies on tendons, which enable movement by transferring forces from muscles to the skeleton. Yet, how load-bearing structures in tendons sense and adapt to physical demands is not understood. Here, by performing calcium (Ca2+) imaging in mechanically loaded tendon explants from rats and in primary tendon cells from rats and humans, we show that tenocytes detect mechanical forces through the mechanosensitive ion channel PIEZO1, which senses shear stresses induced by collagen-fibre sliding. Through tenocyte-targeted loss-of-function and gain-of-function experiments in rodents, we show that reduced PIEZO1 activity decreased tendon stiffness and that elevated PIEZO1 mechanosignalling increased tendon stiffness and strength, seemingly through upregulated collagen cross-linking. We also show that humans carrying the PIEZO1 E756del gain-of-function mutation display a 13.2% average increase in normalized jumping height, presumably due to a higher rate of force generation or to the release of a larger amount of stored elastic energy. Further understanding of the PIEZO1-mediated mechanoregulation of tendon stiffness should aid research on musculoskeletal medicine and on sports performance.
引用
收藏
页码:1457 / 1471
页数:15
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