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 con...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)^(Agc1CreER)mice(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)^(Agc1CreER)mice. 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.展开更多
基金supported by the National Institutes of Health Grants R01 AR054465 and R01 AR070222 to D.Cpartially supported by the Natural Science Foundation of China(NSFC)(grant#81371999)to D.C+2 种基金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
文摘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)^(Agc1CreER)mice(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)^(Agc1CreER)mice. 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.
