Tibial bone compression promotes recovery after brain injury through osteocyte PIEZO1

IF 20.3 1区医学 Q1 NEUROSCIENCES

Nature neuroscience Pub Date : 2026-09-21 DOI:10.1038/s41593-026-02422-w

Zhiqing Cai, Zhimin Zhang, Yuxin Wang, Shencai Liu, Jiarong Leng, Yun Chu, Jihang Liu, Yingying Fang, Bochong Chen, Wenquan Liang, Hong Wang, Lu Zhang, Weiguo Zou, Fan Yang, Qiancheng Song, Di Lu, Xiaochun Bai

{"title":"Tibial bone compression promotes recovery after brain injury through osteocyte PIEZO1","authors":"Zhiqing Cai, Zhimin Zhang, Yuxin Wang, Shencai Liu, Jiarong Leng, Yun Chu, Jihang Liu, Yingying Fang, Bochong Chen, Wenquan Liang, Hong Wang, Lu Zhang, Weiguo Zou, Fan Yang, Qiancheng Song, Di Lu, Xiaochun Bai","doi":"10.1038/s41593-026-02422-w","DOIUrl":null,"url":null,"abstract":"Traumatic brain injury (TBI) accelerates bone healing and induces heterotopic ossification, raising the question of whether an injured brain benefits from bone. Here we reveal that dynamic compressive tibial axial loading (DCTAL), a model of tibial bone compression, increased survival and promoted motor and cognitive recovery after stroke and TBI in mice, as well as in pig TBI models. DCTAL reduced neuron loss, attenuated chronic inflammation and astrogliosis and stimulated neuronal regeneration after TBI. Deletion of the mechanosensory channel Piezo1 in osteocytes reversed these benefits, while serum from DCTAL mice recapitulated them. Osteocytes transduced mechanical signals to directly secrete factors such as IL-1R2, APOL11a and HSP70, while indirectly increasing serum levels of BDNF, PF4 and dopamine. These factors synergistically protected against TBI. Altogether, we establish a bone–brain axis in which bone endocrine function can be modulated by mechanical forces to enhance brain repair after injury.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"17 1","pages":""},"PeriodicalIF":20.3000,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41593-026-02422-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Traumatic brain injury (TBI) accelerates bone healing and induces heterotopic ossification, raising the question of whether an injured brain benefits from bone. Here we reveal that dynamic compressive tibial axial loading (DCTAL), a model of tibial bone compression, increased survival and promoted motor and cognitive recovery after stroke and TBI in mice, as well as in pig TBI models. DCTAL reduced neuron loss, attenuated chronic inflammation and astrogliosis and stimulated neuronal regeneration after TBI. Deletion of the mechanosensory channel Piezo1 in osteocytes reversed these benefits, while serum from DCTAL mice recapitulated them. Osteocytes transduced mechanical signals to directly secrete factors such as IL-1R2, APOL11a and HSP70, while indirectly increasing serum levels of BDNF, PF4 and dopamine. These factors synergistically protected against TBI. Altogether, we establish a bone–brain axis in which bone endocrine function can be modulated by mechanical forces to enhance brain repair after injury.

Abstract Image

查看原文本刊更多论文

胫骨受压通过骨细胞PIEZO1促进脑损伤后的恢复

创伤性脑损伤（TBI）加速骨愈合并诱导异位骨化，这就提出了一个问题，即受伤的大脑是否从骨骼中受益。在这里，我们揭示了动态压缩胫骨轴向负荷（DCTAL），一种胫骨压缩模型，在小鼠和猪TBI模型中增加了中风和TBI后的存活率，并促进了运动和认知的恢复。DCTAL减少了脑外伤后神经元损失，减轻了慢性炎症和星形胶质细胞增生，并刺激了神经元再生。骨细胞中机械感觉通道Piezo1的缺失逆转了这些益处，而DCTAL小鼠的血清再现了这些益处。骨细胞通过机械信号直接分泌IL-1R2、APOL11a、HSP70等因子，同时间接升高血清BDNF、PF4、多巴胺水平。这些因素协同作用防止脑外伤。总之，我们建立了一个骨-脑轴，在这个轴中，骨内分泌功能可以通过机械力来调节，以增强脑损伤后的修复。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature neuroscience 医学-神经科学

CiteScore

38.60

自引率

1.20%

发文量

212

审稿时长

1 months

期刊介绍： Nature Neuroscience, a multidisciplinary journal, publishes papers of the utmost quality and significance across all realms of neuroscience. The editors welcome contributions spanning molecular, cellular, systems, and cognitive neuroscience, along with psychophysics, computational modeling, and nervous system disorders. While no area is off-limits, studies offering fundamental insights into nervous system function receive priority. The journal offers high visibility to both readers and authors, fostering interdisciplinary communication and accessibility to a broad audience. It maintains high standards of copy editing and production, rigorous peer review, rapid publication, and operates independently from academic societies and other vested interests. In addition to primary research, Nature Neuroscience features news and views, reviews, editorials, commentaries, perspectives, book reviews, and correspondence, aiming to serve as the voice of the global neuroscience community.