Cargando…
The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss
Disuse osteoporosis is characterized by decreased bone mass caused by abnormal mechanical stimulation of bone. Piezo1 is a major mechanosensitive ion channel in bone homeostasis. However, whether intervening in the action of Piezo1 can rescue disuse osteoporosis remains unresolved. In this study, a...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646271/ https://www.ncbi.nlm.nih.gov/pubmed/37759400 http://dx.doi.org/10.1002/advs.202303375 |
_version_ | 1785134860387483648 |
---|---|
author | Hu, Yuxiang Tian, Hongtao Chen, Wei Liu, Yunlu Cao, Yulin Pei, Hongxin Ming, Chaochang Shan, Cunqing Chen, Xihui Dai, Zhipeng Yang, Shuhua Shao, Zengwu Lan, Shenghui Liu, Yong Tong, Wei |
author_facet | Hu, Yuxiang Tian, Hongtao Chen, Wei Liu, Yunlu Cao, Yulin Pei, Hongxin Ming, Chaochang Shan, Cunqing Chen, Xihui Dai, Zhipeng Yang, Shuhua Shao, Zengwu Lan, Shenghui Liu, Yong Tong, Wei |
author_sort | Hu, Yuxiang |
collection | PubMed |
description | Disuse osteoporosis is characterized by decreased bone mass caused by abnormal mechanical stimulation of bone. Piezo1 is a major mechanosensitive ion channel in bone homeostasis. However, whether intervening in the action of Piezo1 can rescue disuse osteoporosis remains unresolved. In this study, a commonly‐used hindlimb‐unloading model is employed to simulate microgravity. By single‐cell RNA sequencing, bone marrow‐derived mesenchymal stem cells (BMSCs) are the most downregulated cell cluster, and coincidentally, Piezo1 expression is mostly enriched in those cells, and is substantially downregulated by unloading. Importantly, activation of Piezo1 by systemically‐introducing yoda1 mimics the effects of mechanical stimulation and thus ameliorates bone loss under simulated microgravity. Mechanistically, Piezo1 activation promotes the proliferation and osteogenic differentiation of Gli1(+) BMSCs by activating the β‐catenin and its target gene activating transcription factor 4 (ATF4). Inhibiting β‐catenin expression substantially attenuates the effect of yoda1 on bone loss, possibly due to inhibited proliferation and osteogenic differentiation capability of Gli1(+) BMSCs mediated by ATF4. Lastly, Piezo1 activation also slightly alleviates the osteoporosis of OVX and aged mice. In conclusion, impaired function of Piezo1 in BMSCs leads to insufficient bone formation especially caused by abnormal mechanical stimuli, and is thus a potential therapeutic target for osteoporosis. |
format | Online Article Text |
id | pubmed-10646271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106462712023-09-27 The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss Hu, Yuxiang Tian, Hongtao Chen, Wei Liu, Yunlu Cao, Yulin Pei, Hongxin Ming, Chaochang Shan, Cunqing Chen, Xihui Dai, Zhipeng Yang, Shuhua Shao, Zengwu Lan, Shenghui Liu, Yong Tong, Wei Adv Sci (Weinh) Research Articles Disuse osteoporosis is characterized by decreased bone mass caused by abnormal mechanical stimulation of bone. Piezo1 is a major mechanosensitive ion channel in bone homeostasis. However, whether intervening in the action of Piezo1 can rescue disuse osteoporosis remains unresolved. In this study, a commonly‐used hindlimb‐unloading model is employed to simulate microgravity. By single‐cell RNA sequencing, bone marrow‐derived mesenchymal stem cells (BMSCs) are the most downregulated cell cluster, and coincidentally, Piezo1 expression is mostly enriched in those cells, and is substantially downregulated by unloading. Importantly, activation of Piezo1 by systemically‐introducing yoda1 mimics the effects of mechanical stimulation and thus ameliorates bone loss under simulated microgravity. Mechanistically, Piezo1 activation promotes the proliferation and osteogenic differentiation of Gli1(+) BMSCs by activating the β‐catenin and its target gene activating transcription factor 4 (ATF4). Inhibiting β‐catenin expression substantially attenuates the effect of yoda1 on bone loss, possibly due to inhibited proliferation and osteogenic differentiation capability of Gli1(+) BMSCs mediated by ATF4. Lastly, Piezo1 activation also slightly alleviates the osteoporosis of OVX and aged mice. In conclusion, impaired function of Piezo1 in BMSCs leads to insufficient bone formation especially caused by abnormal mechanical stimuli, and is thus a potential therapeutic target for osteoporosis. John Wiley and Sons Inc. 2023-09-27 /pmc/articles/PMC10646271/ /pubmed/37759400 http://dx.doi.org/10.1002/advs.202303375 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Hu, Yuxiang Tian, Hongtao Chen, Wei Liu, Yunlu Cao, Yulin Pei, Hongxin Ming, Chaochang Shan, Cunqing Chen, Xihui Dai, Zhipeng Yang, Shuhua Shao, Zengwu Lan, Shenghui Liu, Yong Tong, Wei The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss |
title | The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss |
title_full | The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss |
title_fullStr | The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss |
title_full_unstemmed | The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss |
title_short | The Critical Role of The Piezo1/β‐catenin/ATF4 Axis on The Stemness of Gli1(+) BMSCs During Simulated Microgravity‐Induced Bone Loss |
title_sort | critical role of the piezo1/β‐catenin/atf4 axis on the stemness of gli1(+) bmscs during simulated microgravity‐induced bone loss |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646271/ https://www.ncbi.nlm.nih.gov/pubmed/37759400 http://dx.doi.org/10.1002/advs.202303375 |
work_keys_str_mv | AT huyuxiang thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT tianhongtao thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT chenwei thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT liuyunlu thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT caoyulin thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT peihongxin thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT mingchaochang thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT shancunqing thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT chenxihui thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT daizhipeng thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT yangshuhua thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT shaozengwu thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT lanshenghui thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT liuyong thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT tongwei thecriticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT huyuxiang criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT tianhongtao criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT chenwei criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT liuyunlu criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT caoyulin criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT peihongxin criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT mingchaochang criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT shancunqing criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT chenxihui criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT daizhipeng criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT yangshuhua criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT shaozengwu criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT lanshenghui criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT liuyong criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss AT tongwei criticalroleofthepiezo1bcateninatf4axisonthestemnessofgli1bmscsduringsimulatedmicrogravityinducedboneloss |