| INORGANIC MATERIALS AND CERAMIC MATRIX COMPOSITES |
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| The Inhibitory Effect and Mechanism of Aerobic Exercise on the Cytotoxicity of Calcium Phosphate Nanomaterials |
| ZHOU Huiqing1, WANG Yida1, CHEN Xin1, GUO Qing1, CAO Shiqi1, LIU Yuqian1, XIAO Ruilin2,*, LIANG Haixia1,*
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1 College of Artifical Intelligence, Taiyuan University of Technology, Jinzhong 030600, Shanxi, China
2 College of Physical Education and Health Engineering, Taiyuan University of Technology, Jinzhong 030600, Shanxi, China |
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Abstract Calcium phosphate nanoparticles (CaP) exhibit substantial promise in bone defect repair and targeted therapy owing to their exceptional osteoinductivity and controllable degradability. However, the cytotoxicity due to lysosomal membrane permeabilization (LMP) triggered by these nanoparticles remains a key obstacle to their clinical translation. This study illustrates the protective effects of aerobic exercise against CaP-induced lysosomal dysfunction. We show that CaP undergoes rapid degradation in the acidic lysosomal milieu, which leads to the release of abundant Ca2+ ions that elevate lysosomal pH and enhance LMP, thereby destabilizing the lysosomal membrane. The aerobic exercise mimetic AICAR effectively mitigates this toxicity by upregulating VMA21 expression, promoting the assembly of V0/V1 subunits of V-ATPase (vacuolar-type ATPase), and reinforcing lysosomal membrane stability to suppress LMP. Mechanistically, AICAR activates the AMPK signaling pathway to restore the lysosomal proton gradient and counteract Ca2+-induced osmotic imbalance, thereby preserving lysosomal integrity. At the animal le-vel, aerobic exercise alleviates CaP-induced histopathological damage in multiple organs and restores serum markers of liver and kidney injury to normal levels. These findings provide a novel "endogenous defense" strategy for optimizing the biosafety of calcium phosphate nanoparticles (CaP), driving a paradigm shift in nanomedicine from "passive toxicity inhibition" to "exercise-modulated intervention".
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Published: 10 August 2025
Online: 2025-08-13
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2025, Vol. 39 
