Bone & joint research · 2026
Exercise-primed Trpv4+ progenitors sense mechanical to regulate graded transition in enthesis regeneration.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xu Shibo, Lin Yiyi, Yu Yihang, Zhu Zhiquan, Huang Pan, Xie Qizhong, Chen Yujianan, Tao Xu, Zhou Mei, Liu Zunhan, Bian Xuting, Guo Lin
Аннотация
AIMS: To identify the molecular mechanisms of mechanotransduction that drive functional regeneration rather than scar formation at the tendon-bone interface, addressing the high clinical failure rates of enthesis injuries.
METHODS: Single-cell RNA sequencing was performed on enthesis tissues at multiple post-injury timepoints. A mouse tendon-bone insertion injury model was established with treadmill exercise versus sedentary controls. Transient receptor potential vanilloid 4 (TRPV4)+ cells were isolated by fluorescence-activated cell sorting for functional assays. Mechanistic studies included bulk RNA sequencing, immunofluorescence, and in vitro mechanical stimulation. Functional outcomes were assessed by histomorphometry, micro-CT, and biomechanical testing.
RESULTS: Single-cell transcriptomics identified Trpv4+ cells specifically enriched in chondrogenic lineages during enthesis repair. Mechanical stimulation significantly increased Trpv4+ chondrocyte density and enhanced chondrogenic marker expression. Lineage tracing confirmed that Trpv4+ progenitors possess clonogenicity and multipotent differentiation capacity, with mechanical stimulation enhancing their chondrogenic potential. Mechanistically, Trpv4 activation facilitated calcium influx, leading to calcineurin-NFATc1 signalling cascade activation. Transplantation of exercise-primed Trpv4+ progenitor cells significantly improved cartilage matrix deposition and biomechanical properties compared to controls.
CONCLUSION: Trpv4 + progenitors constitute a mechanosensitive population critical for enthesis regeneration. Exercise enhances Trpv4-dependent chondrogenic differentiation through the calcium-calcineurin-NFATc1 axis, providing a scientific basis for optimizing postoperative rehabilitation.
METHODS: Single-cell RNA sequencing was performed on enthesis tissues at multiple post-injury timepoints. A mouse tendon-bone insertion injury model was established with treadmill exercise versus sedentary controls. Transient receptor potential vanilloid 4 (TRPV4)+ cells were isolated by fluorescence-activated cell sorting for functional assays. Mechanistic studies included bulk RNA sequencing, immunofluorescence, and in vitro mechanical stimulation. Functional outcomes were assessed by histomorphometry, micro-CT, and biomechanical testing.
RESULTS: Single-cell transcriptomics identified Trpv4+ cells specifically enriched in chondrogenic lineages during enthesis repair. Mechanical stimulation significantly increased Trpv4+ chondrocyte density and enhanced chondrogenic marker expression. Lineage tracing confirmed that Trpv4+ progenitors possess clonogenicity and multipotent differentiation capacity, with mechanical stimulation enhancing their chondrogenic potential. Mechanistically, Trpv4 activation facilitated calcium influx, leading to calcineurin-NFATc1 signalling cascade activation. Transplantation of exercise-primed Trpv4+ progenitor cells significantly improved cartilage matrix deposition and biomechanical properties compared to controls.
CONCLUSION: Trpv4 + progenitors constitute a mechanosensitive population critical for enthesis regeneration. Exercise enhances Trpv4-dependent chondrogenic differentiation through the calcium-calcineurin-NFATc1 axis, providing a scientific basis for optimizing postoperative rehabilitation.