ASIC3 roles in mechanosensitive elongation of nucleus pulposus cells

Jormay Lim; Shao-Shiang Huang; Mohammad Nikkhoo; Wei-Ting Tai; Ya-Cherng Chu; Andy Chien; Jaw-Lin Wang

doi:10.1016/j.jbiomech.2024.111938

ASIC3 roles in mechanosensitive elongation of nucleus pulposus cells

J Biomech. 2024 Jan:163:111938. doi: 10.1016/j.jbiomech.2024.111938. Epub 2024 Jan 10.

Authors

Jormay Lim¹, Shao-Shiang Huang¹, Mohammad Nikkhoo², Wei-Ting Tai¹, Ya-Cherng Chu³, Andy Chien¹, Jaw-Lin Wang⁴

Affiliations

¹ Department of Biomedical Engineering, College of Medicine and College of Engineering, Nation Taiwan University, Taipei, Taiwan.
² Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Department of Biomedical Engineering, College of Medicine and College of Engineering, Nation Taiwan University, Taipei, Taiwan; Center of Medical Devices, National Taiwan University, Taipei, Taiwan.
⁴ Department of Biomedical Engineering, College of Medicine and College of Engineering, Nation Taiwan University, Taipei, Taiwan; Center of Medical Devices, National Taiwan University, Taipei, Taiwan. Electronic address: jlwang@ntu.edu.tw.

PMID: 38217980
DOI: 10.1016/j.jbiomech.2024.111938

Abstract

Morphological changes of the nucleus pulposus (NP) cells occur concomitantly as part of the intervertebral disc (IVD) degeneration and excessive mechanical loading has been speculated as a significant key factor for contributing to such morphological changes. Therefore, we hypothesize that stress exerted on NP cells can cause a deformity of nucleus in response. The changes of cell morphology is observed in degenerative nucleus pulposus. One of the reasons for degeneration of NP is due to overloading of NP especially in the obese population. So the nucleus deformity caused by stress/force is of our study interest. To delineate the effects and role of mechanical stress, we developed a 3D assay using hydrogel cultures with a circular hole generated with needle indentation to simulate a local stress concentration along the edge of the hole. A stressed zone, encompassing 100 μm of range from the circular edge, is defined based on stress concentration calculation to enable quantitative analysis against the control zone. Our results demonstrated that the circular hole produces stress-induced morphological changes in NP cells. The tangential elongation of NP cells and their nucleus shape changes in the stressed zone are significantly increased compared to the non-stressed control zone. It is proposed that the cell elongation is a direct response to elevated stress within the stressed zone. Subsequently we found the stress induced morphological changes of the NP cells can be significantly reduced by inhibiting ASIC3. This suggests ASIC3 plays an important role of play in mechano-signaling of NP cells.

Keywords: 3D culture; ASIC3; Mechano-signaling; Nucleus pulposus.

MeSH terms

Acid Sensing Ion Channels
Cells, Cultured
Humans
Intervertebral Disc Degeneration*
Intervertebral Disc*
Nucleus Pulposus* / physiology

Substances

ASIC3 protein, human
Acid Sensing Ion Channels