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Original Article | Open Access

Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain

Ke Lu1,2, Qingyun Wang1,2, Hua Jiang3, Jun Li4, Zhou Yao5, Yongcan Huang6, Jianquan Chen7, Yejia Zhang4,8, Guozhi Xiao9, Xueyu Hu5, Zhuojing Luo5, Liu Yang5, Liping Tong1, Di Chen1,2( )
Research Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
Division of Spine Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Institute of Orthopedics, Xijing Hospital, the Fourth Military Medical University, Xi’an, China
Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, China
Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, China
Departments of Physical Medicine & Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
School of Medicine, Southern University of Science and Technology, Shenzhen, China
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Abstract

Spine degeneration is an aging-related disease, but its molecular mechanisms remain unknown, although elevated β-catenin signaling has been reported to be involved in intervertebral disc degeneration. Here, we determined the role of β-catenin signaling in spinal degeneration and in the homeostasis of the functional spinal unit (FSU), which includes the intervertebral disc, vertebra and facet joint and is the smallest physiological motion unit of the spine. We showed that pain sensitivity in patients with spinal degeneration is highly correlated with β-catenin protein levels. We then generated a mouse model of spinal degeneration by transgenic expression of constitutively active β-catenin in Col2+ cells. We found that β-catenin-TCF7 activated the transcription of CCL2, a known critical factor in osteoarthritic pain. Using a lumbar spine instability model, we showed that a β-catenin inhibitor relieved low back pain. Our study indicates that β-catenin plays a critical role in maintaining spine tissue homeostasis, its abnormal upregulation leads to severe spinal degeneration, and its targeting could be an avenue to treat this condition.

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Bone Research
Volume 11,
December 2023
Article number: 18
DOI: 10.1038/s41413-023-00253-0
Cite this article:
Lu K, Wang Q, Jiang H, et al. Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain. Bone Research, 2023, 11: 18. https://doi.org/10.1038/s41413-023-00253-0

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Received: 07 October 2022
Revised: 21 January 2023
Accepted: 10 February 2023
Published: 14 April 2023
© The Author(s) 2023

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