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

作　　者：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 

机构地区：[1]Research Center for Computer-aided Drug Discovery,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,China [2]Faculty of Pharmaceutical Sciences,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,China [3]Division of Spine Surgery,the First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi,China [4]Department of Orthopedic Surgery,Perelman School of Medicine,University of Pennsylvania,Philadelphia,PA,USA [5]Institute of Orthopedics,Xijing Hospital,the Fourth Military Medical University,Xi’an,China [6]Department of Spine Surgery,Peking University Shenzhen Hospital,Shenzhen,China [7]Department of Clinical Medicine,School of Medicine,Zhejiang University City College,Hangzhou,Zhejiang,China [8]Departments of Physical Medicine&Rehabilitation,Perelman School of Medicine,University of Pennsylvania,PA,USA [9]School of Medicine,Southern University of Science and Technology,Shenzhen,China

出　　处：《Bone Research》2023年第2期316-327,共12页骨研究（英文版）

基　　金：supported by the National Key Research and Development Program of China(2021YFB3800800)to L.T.and D.C.;supported by the National Natural Science Foundation of China(NSFC)grants 82030067,82161160342,and 82250710174 to D.C.;NSFC grant 82172397 to L.T.;supported by the Chinese Postdoctoral Science Foundation(2022M710158)。

摘　　要：Spine degeneration is an aging-related disease,but its molecular mechanisms remain unknown,although elevatedβ-catenin signaling has been reported to be involved in intervertebral disc degeneration.Here,we determined the role ofβ-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 withβ-catenin protein levels.We then generated a mouse model of spinal degeneration by transgenic expression of constitutively activeβ-catenin in Col2^(+) cells.We found thatβ-catenin-TCF7 activated the transcription of CCL2,a known critical factor in osteoarthritic pain.Using a lumbar spine instability model,we showed that aβ-catenin inhibitor relieved low back pain.Our study indicates thatβ-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.

关 键 词：DEGENERATION smallest HOMEOSTASIS 

分 类 号：R681.5[医药卫生—骨科学]