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ORIGINAL RESEARCH article

Front. Med.
Sec. Pathology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1531907
This article is part of the Research Topic Regulation of intervertebral disc homeostasis and the pathological or pathophysiological alterations under various harmful stimuli during aging process View all articles

Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis

Provisionally accepted
Junxian Hu Junxian Hu Yibo Zhu Yibo Zhu zeyu Pang zeyu Pang Xiaoxiao Li Xiaoxiao Li Huilin Zhang Huilin Zhang Xiangwei Li Xiangwei Li Yongjian Gao Yongjian Gao Yiyang Wang Yiyang Wang *Pei Li Pei Li *Qiang Zhou Qiang Zhou *
  • Third Affiliated Hospital of Chongqing Medical University, Chongqing, China

The final, formatted version of the article will be published soon.

    The low hydrostatic pressure in the intervertebral disc plays a crucial role in maintaining the homeostasis of the disc environment, particularly in supporting the physiological functions of nucleus pulposus cells (NPCs). However, the underlying mechanisms remain poorly understood. TRPV4, a baroreceptor in the intervertebral disc, is primarily responsible for converting extracellular pressure signals into intracellular chemical signals. Upon activation, TRPV4 facilitates the influx of calcium ions, thereby regulating the physiological behavior of NP cells. Calreticulin (CRT), an endoplasmic reticulum retention protein, performs various physiological functions, including the regulation of intracellular calcium levels. CRT also exhibits distinct roles depending on its subcellular localization. In this study, we observed that under low hydrostatic pressure, TRPV4 activation and subsequent calcium influx led to an increase in CRT synthesis and a significant rise in its cytosolic expression. This was followed by the depolymerization of focal adhesion (FA) complexes, primarily consisting of FAK and integrin β1, which resulted in an increase in collagen type II (Col II) and a decrease in collagen type I (Col I). These changes in extracellular matrix (ECM) composition helped maintain the physiological function of NP cells. Furthermore, overexpression of CRT enhanced the ability of NP cells to resist partial functional damage caused by high hydrostatic pressure. Taken together, our findings suggested that low hydrostatic pressure enhanced NP cell function by regulating the TRPV4/CRT/FA complex signaling axis.

    Keywords: Intervertebral discs, Nucleus pulposus cell, Hydrostatic Pressure, Calreticulin, cellular functional homeostasis

    Received: 21 Nov 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Hu, Zhu, Pang, Li, Zhang, Li, Gao, Wang, Li and Zhou. 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:
    Yiyang Wang, Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
    Pei Li, Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
    Qiang Zhou, Third Affiliated Hospital of Chongqing Medical University, Chongqing, China

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