Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis
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 barorece...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1531907/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Junxian Hu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-518e0f62bfda4f599bab1a4fc1248948 |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj-art-518e0f62bfda4f599bab1a4fc12489482025-01-29T06:45:37ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011210.3389/fmed.2025.15319071531907Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axisJunxian Hu0Junxian Hu1Yibo Zhu2Yibo Zhu3Zeyu Pang4Zeyu Pang5Xiaoxiao Li6Xiaoxiao Li7Huilin Zhang8Huilin Zhang9Xiangwei Li10Xiangwei Li11Yongjian Gao12Yongjian Gao13Yiyang Wang14Yiyang Wang15Pei Li16Pei Li17Qiang Zhou18Qiang Zhou19Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaTissue Repairing and Biotechnology Research Center, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fmed.2025.1531907/fullintervertebral discsnucleus pulposus cellhydrostatic pressurecalreticulincellular functional homeostasis |
| spellingShingle | 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 Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis Frontiers in Medicine intervertebral discs nucleus pulposus cell hydrostatic pressure calreticulin cellular functional homeostasis |
| title | Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis |
| title_full | Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis |
| title_fullStr | Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis |
| title_full_unstemmed | Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis |
| title_short | Low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the TRPV4/CRT/FA complex axis |
| title_sort | low hydrostatic pressure promotes functional homeostasis of nucleus pulposus cells through the trpv4 crt fa complex axis |
| topic | intervertebral discs nucleus pulposus cell hydrostatic pressure calreticulin cellular functional homeostasis |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1531907/full |
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