The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance

Ryo Nakamichi, Shang Ma, Takayuki Nonoyama, Tomoki Chiba, Ryota Kurimoto, Hiroki Ohzono, Merissa Olmer, Chisa Shukunami, Noriyuki Fuku, Guan Wang, Errol Morrison, Yannis Pitsiladis, Toshifumi Ozaki, Darryl D'Lima, Martin Lotz, Ardem Patapoutian, Hiroshi Asahara

Research output: Contribution to journalArticlepeer-review


How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1, a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice. These phenotypes were associated with enhanced tendon anabolism via an increase in tendon-specific transcription factors, Mohawk and Scleraxis, but there was no evidence of changes in muscle. Biomechanical analysis showed that the tendons of R2482H Piezo1 mice were more compliant and stored more elastic energy, consistent with the enhancement of jumping ability. These phenotypes were replicated in mice with tendon-specific R2482H Piezo1 replacement after tendon maturation, indicating that PIEZO1 could be a target for promoting physical performance by enhancing function in mature tendon. The frequency of E756del PIEZO1 was higher in sprinters than in population-matched nonathletic controls in a small Jamaican co-hort, suggesting a similar function in humans. Together, this human and mouse genetic and physiological evidence revealed a critical function of tendons in physical performance, which is tightly and robustly regulated by
PIEZO1 in tenocytes.
Original languageEnglish
Article numbereabj5557
Number of pages15
JournalScience Translational Medicine
Issue number647
Publication statusPublished - 1 Jun 2022


  • Animals
  • Ion Channels - genetics
  • Mice
  • Physical Functional Performance
  • Stress, Mechanical
  • Tendons - metabolism
  • Transcription Factors


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