LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis

Abstract Osteoarthritis (OA) is a degenerative disease which places an enormous burden on society, effective treatments are still limited. As a non‐invasive and safe physical therapy, low‐intensity pulsed ultrasound (LIPUS) can alleviate OA progression, but the underlying mechanism is not fully unde...

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Main Authors: Mengtong Guan, Xiaoyu Han, Bo Liao, Wang Han, Lin Chen, Bin Zhang, Xiuqin Peng, Yu Tian, Gongyi Xiao, Xinhe Li, Liang Kuang, Ying Zhu, Dingqun Bai
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202413930
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author Mengtong Guan
Xiaoyu Han
Bo Liao
Wang Han
Lin Chen
Bin Zhang
Xiuqin Peng
Yu Tian
Gongyi Xiao
Xinhe Li
Liang Kuang
Ying Zhu
Dingqun Bai
author_facet Mengtong Guan
Xiaoyu Han
Bo Liao
Wang Han
Lin Chen
Bin Zhang
Xiuqin Peng
Yu Tian
Gongyi Xiao
Xinhe Li
Liang Kuang
Ying Zhu
Dingqun Bai
author_sort Mengtong Guan
collection DOAJ
description Abstract Osteoarthritis (OA) is a degenerative disease which places an enormous burden on society, effective treatments are still limited. As a non‐invasive and safe physical therapy, low‐intensity pulsed ultrasound (LIPUS) can alleviate OA progression, but the underlying mechanism is not fully understood, especially the mechanical transduction between LIPUS and the organism. In this pioneering study, the biomechanical effects of LIPUS on living mice chondrocytes and living body zebrafish are investigate by using fluorescence imaging technology, to dynamically “visualize” its invisible mechanical stimuli in the form of calcium oscillations. It is also confirmed that LIPUS maintains cartilage homeostasis by promoting chondrocyte autophagy in a calcium‐dependent manner. In addition, chondrocyte ion channels are screened by scRNA‐seq and confirm that the mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) mediated the biological effects of LIPUS on chondrocytes. Finally, it is found that a combination of pharmacologically induced and LIPUS‐induced Ca2+ influx in chondrocytes enhances the cartilage‐protective effect of LIPUS, which may provide new insights for optimizing LIPUS in the treatment of OA.
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spelling doaj-art-9f0e46a420a84b1a9cdf36e47058d39c2025-08-20T03:14:12ZengWileyAdvanced Science2198-38442025-04-011216n/an/a10.1002/advs.202413930LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate OsteoarthritisMengtong Guan0Xiaoyu Han1Bo Liao2Wang Han3Lin Chen4Bin Zhang5Xiuqin Peng6Yu Tian7Gongyi Xiao8Xinhe Li9Liang Kuang10Ying Zhu11Dingqun Bai12Department of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaCenter of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 ChinaCenter of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 ChinaCenter of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 ChinaCenter of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 ChinaDepartment of Orthopedics Chonggang General Hospital Chongqing 400000 ChinaDepartment of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaCenter of Bone Metabolism and repair laboratory for Prevention and rehabilitation of Training injuries State Key laboratory of Trauma Burns and combined injury Trauma center Research Institute of Surgery Daping Hospital Army Medical University (Third Military Medical University) Chongqing 400000 ChinaDepartment of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Rehabilitation Medicine Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission The First Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaAbstract Osteoarthritis (OA) is a degenerative disease which places an enormous burden on society, effective treatments are still limited. As a non‐invasive and safe physical therapy, low‐intensity pulsed ultrasound (LIPUS) can alleviate OA progression, but the underlying mechanism is not fully understood, especially the mechanical transduction between LIPUS and the organism. In this pioneering study, the biomechanical effects of LIPUS on living mice chondrocytes and living body zebrafish are investigate by using fluorescence imaging technology, to dynamically “visualize” its invisible mechanical stimuli in the form of calcium oscillations. It is also confirmed that LIPUS maintains cartilage homeostasis by promoting chondrocyte autophagy in a calcium‐dependent manner. In addition, chondrocyte ion channels are screened by scRNA‐seq and confirm that the mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) mediated the biological effects of LIPUS on chondrocytes. Finally, it is found that a combination of pharmacologically induced and LIPUS‐induced Ca2+ influx in chondrocytes enhances the cartilage‐protective effect of LIPUS, which may provide new insights for optimizing LIPUS in the treatment of OA.https://doi.org/10.1002/advs.202413930autophagycalcium signalingchondrocyteslow‐intensity pulsed ultrasoundosteoarthritis
spellingShingle Mengtong Guan
Xiaoyu Han
Bo Liao
Wang Han
Lin Chen
Bin Zhang
Xiuqin Peng
Yu Tian
Gongyi Xiao
Xinhe Li
Liang Kuang
Ying Zhu
Dingqun Bai
LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis
Advanced Science
autophagy
calcium signaling
chondrocytes
low‐intensity pulsed ultrasound
osteoarthritis
title LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis
title_full LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis
title_fullStr LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis
title_full_unstemmed LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis
title_short LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis
title_sort lipus promotes calcium oscillation and enhances calcium dependent autophagy of chondrocytes to alleviate osteoarthritis
topic autophagy
calcium signaling
chondrocytes
low‐intensity pulsed ultrasound
osteoarthritis
url https://doi.org/10.1002/advs.202413930
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