ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1625333
This article is part of the Research TopicMechanopathology: Unraveling the Mechanical Forces Driving Disease MechanismsView all 3 articles
The mechanosensitive protein ANTXR1 is involved in maintaining cartilage homeostasis in post-traumatic osteoarthritis
Provisionally accepted
Zhuangzhuang Miao1
Junjie Liu1
Pengfei Cheng1
Yinghao Shen1
Jiahang Tang1Jiajie Zhu2Weiwei Liu1
Xuchang Zhou3*Hongying Jing1- 1Harbin Sport University, harbin, China
- 2shandong sport University, jinan, China
- 3Beijing Sport University, Beijing, China
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Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease secondary to joint trauma, such as anterior cruciate ligament (ACL) injury. Our previous study found that the mechanosensitive protein ANTXR1 is involved in the regulation of bone homeostasis, however, whether ANTXR1 is involved in the regulation of cartilage homeostasis in PTOA is unclear. In this study, we focused on the expression of the mechanosensitive protein ANTXR1 in cartilage homeostasis and explored its role in the initiation and progression of PTOA. To investigate the effects of treadmill exercise on bone-cartilage homeostasis, we established models using different exercise intensities (20%, 40%, 60%, 80% of maximal oxygen uptake, VO₂max). Histological staining (Hematoxylin and Eosin, HE) and micro-computed tomography (micro-CT) revealed that moderate-intensity exercise (40%-60% VO₂max) effectively promoted bone-cartilage health compared to controls. Conversely, prolonged high-intensity exercise (8 weeks, 80% VO₂max) demonstrated potentially deleterious effects on cartilage homeostasis. Immunofluorescence staining indicated that, compared to the sedentary group, both ANTXR1 protein expression in the 2 knee cartilage was reduced across intervention groups, with expression levels progressively declining as exercise intensity increased. Notably, ANTXR1 and exhibited significantly higher expression in bone tissue compared to cartilage tissue. Bioinformatic analysis identified LRP6 as a potential target protein of ANTXR1. Furthermore, utilizing a post-traumatic osteoarthritis (PTOA) animal model, we explored the potential role of ANTXR1 in cartilage homeostasis and revealed that both ANTXR1 and LRP6 protein expression were significantly up-regulated in the degenerating cartilage of PTOA rats. This study is the first to elucidate the dual roles of ANTXR1 in mechano-signaling and cartilage metabolic homeostasis, providing a molecular basis for developing ANTXR1-targeting inhibitors for PTOA treatment.
Keywords: Osteoarthritis, ANTXR1, LRP6, treadmill exercise, Anterior cruciate ligament Osteoarthritis, Anterior cruciate ligament injury
Received: 09 May 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Miao, Liu, Cheng, Shen, Tang, Zhu, Liu, Zhou and Jing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xuchang Zhou, Beijing Sport University, Beijing, China
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