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

• Published in: Bone Research Vol. 11; no. 1; pp. 18 - 327
• Main Authors: Lu, Ke, Wang, Qingyun, Jiang, Hua, Li, Jun, Yao, Zhou, Huang, Yongcan, Chen, Jianquan, Zhang, Yejia, Xiao, Guozhi, Hu, Xueyu, Luo, Zhuojing, Yang, Liu, Tong, Liping, Chen, Di
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.04.2023; Springer Nature B.V; Research Center for Computer-aided Drug Discovery,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,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%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%Department of Orthopedic Surgery,Perelman School of Medicine,University of Pennsylvania,Philadelphia,PA,USA; Nature Publishing Group
• Subjects: 631/443/63; 692/420; Homeostasis; Internal Medicine; Medicine; Medicine & Public Health; Orthopedics
• ISSN: 2095-4700; 2095-6231
• DOI: 10.1038/s41413-023-00253-0

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.