Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain
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 home...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-023-00253-0 |
| _version_ | 1797846063236775936 |
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| author | Ke Lu Qingyun Wang Hua Jiang Jun Li Zhou Yao Yongcan Huang Jianquan Chen Yejia Zhang Guozhi Xiao Xueyu Hu Zhuojing Luo Liu Yang Liping Tong Di Chen |
| author_facet | Ke Lu Qingyun Wang Hua Jiang Jun Li Zhou Yao Yongcan Huang Jianquan Chen Yejia Zhang Guozhi Xiao Xueyu Hu Zhuojing Luo Liu Yang Liping Tong Di Chen |
| author_sort | Ke Lu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T17:48:57Z |
| format | Article |
| id | doaj.art-1aeee8debffd4c44a91a31f8c70b7b0d |
| institution | Directory Open Access Journal |
| issn | 2095-6231 |
| language | English |
| last_indexed | 2024-04-09T17:48:57Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj.art-1aeee8debffd4c44a91a31f8c70b7b0d2023-04-16T11:09:08ZengNature Publishing GroupBone Research2095-62312023-04-0111111210.1038/s41413-023-00253-0Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and painKe Lu0Qingyun Wang1Hua Jiang2Jun Li3Zhou Yao4Yongcan Huang5Jianquan Chen6Yejia Zhang7Guozhi Xiao8Xueyu Hu9Zhuojing Luo10Liu Yang11Liping Tong12Di Chen13Research Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesResearch Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesDivision of Spine Surgery, the First Affiliated Hospital of Guangxi Medical UniversityDepartment of Orthopedic Surgery, Perelman School of Medicine, University of PennsylvaniaInstitute of Orthopedics, Xijing Hospital, the Fourth Military Medical UniversityDepartment of Spine Surgery, Peking University Shenzhen HospitalDepartment of Clinical Medicine, School of Medicine, Zhejiang University City CollegeDepartment of Orthopedic Surgery, Perelman School of Medicine, University of PennsylvaniaSchool of Medicine, Southern University of Science and TechnologyInstitute of Orthopedics, Xijing Hospital, the Fourth Military Medical UniversityInstitute of Orthopedics, Xijing Hospital, the Fourth Military Medical UniversityInstitute of Orthopedics, Xijing Hospital, the Fourth Military Medical UniversityResearch Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesResearch Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1038/s41413-023-00253-0 |
| spellingShingle | Ke Lu Qingyun Wang Hua Jiang Jun Li Zhou Yao Yongcan Huang Jianquan Chen Yejia Zhang Guozhi Xiao Xueyu Hu Zhuojing Luo Liu Yang Liping Tong Di Chen Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain Bone Research |
| title | Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain |
| title_full | Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain |
| title_fullStr | Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain |
| title_full_unstemmed | Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain |
| title_short | Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain |
| title_sort | upregulation of β catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain |
| url | https://doi.org/10.1038/s41413-023-00253-0 |
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