Activation of β-catenin signaling in aggrecan-expressing cells in temporomandibular joint causes osteoarthritis-like defects  

作　　者：Tianqian Hui Yachuan Zhou Tingyu Wang Jun Li Shanxing Zhang Lifan Liao Jianhong Gu Ling Ye Lan Zhao Di Chen 

机构地区：[1]Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology [2]State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University [3]Department of Orthopaedic Surgery, Rush University Medical Center [4]Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine [5]Department of Medical Cell Biology and Genetics, Shenzhen Key Laboratory and the Center for Anti-Ageing and Regenerative Medicine, Shenzhen University Medical School

出　　处：《International Journal of Oral Science》2018年第2期102-109,共8页国际口腔科学杂志（英文版）

基　　金：supported by the National Institutes of Health Grants R01 AR054465 and R01 AR070222 to D.C;partially supported by the Natural Science Foundation of China(NSFC)(grant#81371999)to D.C;partially supported by the State Scholarship Fund(No.201406240061);partially sponsored by a grant from Shenzhen Science and Technology Innovation Committee(JCYJ20160331114205502 and JCYJ20150626090344603);partially supported by NSFC grants(grant#81301531 and 81572104),China

摘　　要：β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis（OA） development in temporomandibular joint（TMJ）, we have generated β-catenin conditional activation mice（β-cat（ex3）^Agc1CreER）by breeding Agc1-CreER mice with β-catenin^flox（ex3/＋）mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat（ex3）^Agc1CreERmice（tamoxifen induction was performed at 2 weeks of age）, including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat（ex3）^（Col2CreER）mice, β-cat（ex3）^（Agc1CreER）mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat（ex3）^（Agc1CreER）mice. Results of proliferating cell nuclear antigen（PCNA）, Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling（TUNEL） staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat（ex3）^Agc1CreERmice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis（OA） development in temporomandibular joint（TMJ）, we have generated β-catenin conditional activation mice（β-cat（ex3）^Agc1CreER）by breeding Agc1-CreER mice with β-catenin^flox（ex3/＋）mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat（ex3）^Agc1CreERmice（tamoxifen induction was performed at 2 weeks of age）, including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat（ex3）^（Col2CreER）mice, β-cat（ex3）^（Agc1CreER）mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat（ex3）^（Agc1CreER）mice. Results of proliferating cell nuclear antigen（PCNA）, Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling（TUNEL） staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat（ex3）^Agc1CreERmice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.

关 键 词：TMJ OA ACTIVATION 

分 类 号：R318.08[医药卫生—生物医学工程] R329.25[医药卫生—基础医学]