Hu Junxian, Zhu Yibo, Pang Zeyu, Li Xiaoxiao, Zhang Huilin, Li Xiangwei, Gao Yongjian, Wang Yiyang, Li Pei, Zhou Qiang
Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Tissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Med (Lausanne). 2025 Jan 29;12:1531907. doi: 10.3389/fmed.2025.1531907. eCollection 2025.
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.
椎间盘内的低静水压在维持椎间盘环境的稳态中起着关键作用，尤其是在支持髓核细胞（NPCs）的生理功能方面。然而，其潜在机制仍知之甚少。TRPV4是椎间盘中的一种压力感受器，主要负责将细胞外压力信号转化为细胞内化学信号。激活后，TRPV4促进钙离子内流，从而调节NP细胞的生理行为。钙网蛋白（CRT）是一种内质网驻留蛋白，具有多种生理功能，包括调节细胞内钙水平。CRT根据其亚细胞定位也表现出不同的作用。在本研究中，我们观察到在低静水压下，TRPV4激活及随后的钙内流导致CRT合成增加及其胞质表达显著升高。随后，主要由FAK和整合素β1组成的粘着斑（FA）复合物解聚，导致II型胶原（Col II）增加和I型胶原（Col I）减少。细胞外基质（ECM）组成的这些变化有助于维持NP细胞的生理功能。此外，CRT的过表达增强了NP细胞抵抗高静水压引起的部分功能损伤的能力。综上所述，我们的研究结果表明，低静水压通过调节TRPV4/CRT/FA复合物信号轴增强了NP细胞的功能。
