Effect and mechanism of mechanical factors on intervertebral disc degeneration

doi:10.12307/2022.501

Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (12): 1816-1821.doi: 10.12307/2022.501

Effect and mechanism of mechanical factors on intervertebral disc degeneration

Yin Xunlu1, Jin Zhefeng1, Zhu Liguo1, 2, 3, Feng Minshan1, 2, 3, Yu Jie1, Wei Xu1, Zhan Jiawen1, Gao Chunyu1, Yin He1, Liang Long4, Han Tao1, Sun Kai1, Xie Rui1

1Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100102, China; 2Beijing Institute of Integrated Traditional Chinese and Western Medicine, Beijing 100700, China; 3Beijing Key Laboratory of Bone Setting Technology of Traditional Chinese Medicine, Beijing 100700, China; 4First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, Anhui Province, China

Received:2021-06-02 Revised:2021-06-17 Accepted:2021-07-10 Online:2022-04-28 Published:2021-12-14
Contact: Jin Zhefeng, Master, Associte chief physician, Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100102, China Feng Minshan, MD, Chief physician, Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100102, China; Beijing Institute of Integrated Traditional Chinese and Western Medicine, Beijing 100700, China; Beijing Key Laboratory of Bone Setting Technology of Traditional Chinese Medicine, Beijing 100700, China
About author:Yin Xunlu, MD, Attending physician, Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100102, China Zhu Liguo, MD, Chief physician, Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing 100102, China; Beijing Institute of Integrated Traditional Chinese and Western Medicine, Beijing 100700, China; Beijing Key Laboratory of Bone Setting Technology of Traditional Chinese Medicine, Beijing 100700, China Yin Xunlu and Zhu Liguo contributed equally to this article.
Supported by:
the National Natural Science Foundation of China, No. 81774330 (to FMS); Beijing Natural Science Foundation (Youth Project), No. 7214297 (to YXL)

Abstract

Abstract: BACKGROUND: Our previous study found that mechanical stimulation can affect many key proteins in the Wnt/β-catenin signaling pathway (including β-catenin and GSK-3β protein), but whether it regulates the Wnt/β-catenin signaling pathway in nucleus pulposus cells remains to be clarified.
OBJECTIVE: To clarify the characteristics and effect of continuous loading pressure on intervertebral disc degeneration, and explore the mechanism of mechanical factors-mediated Wnt/β-catenin signaling pathway on intervertebral disc degeneration.
METHODS: Seventy New Zealand white rabbits were selected to establish a rabbit spinal motion segment model, which were randomly divided into blank control group (0 kg), low pressure group (0.5 kg), medium pressure group (1 kg), and high pressure group (3 kg) according to the sustained loading pressure. Others were divided into control group by using optimal sustained loading pressure, activator group and inhibitor group by using Wnt/β-catenin specific activators (SB216763) and inhibitors (ICG001), for 3 consecutive days. Hematoxylin-eosin staining, DAB staining, western blot assay, and RT-PCR were used to observe the function of nucleus pulposus cells. The protocols were approved by Medical Ethics Committee of Wangjing Hospital, China Academy of Chinese Medical Sciences.
RESULTS AND CONCLUSION: (1) The survival rate of nucleus pulposus cells was high under medium pressure (1 kg). Sustained loading pressure could induce intervertebral disc degeneration at 3 days. (2) Compared with the control group, the number of nucleus pulposus cells in the activator group was significantly increased; the cell morphology was regular, and the fibrous tissue and scar in the nucleus pulposus were not obvious. The expression levels of β-catenin and Aggrecan protein were higher and the experssion of GSK-3β protein was significantly decreased (P < 0.05). The expression levels of Aggrecan and Collagen II mRNA were significantly increased (P < 0.05). (3) Compared with the control group, the number of nucleus pulposus cells in the inhibitor group was significantly reduced; the cell morphology was fusiform, and the fibrous tissue and scar in the nucleus pulposus were more obvious; the expression levels of GSK-3β and β-catenin were not significantly different, but the expression of Aggrecan and Collagen II mRNA decreased significantly (P < 0.05). (4) It is concluded that sustained loading force regulates the process of intervertebral disc degeneration in nucleus pulposus cells by mediating Wnt/β-catenin signaling pathway.

Key words: lumbar disc herniation, intervertebral disc degeneration, continuous load pressure, nucleus pulposus cells, Wnt/β-catenin signaling pathway

CLC Number:

Yin Xunlu, Jin Zhefeng, Zhu Liguo, Feng Minshan, Yu Jie, Wei Xu, Zhan Jiawen, Gao Chunyu, Yin He, Liang Long, Han Tao, Sun Kai, Xie Rui . Effect and mechanism of mechanical factors on intervertebral disc degeneration[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(12): 1816-1821.

Figures/Tables 6

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Effect and mechanism of mechanical factors on intervertebral disc degeneration

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