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

Abstract 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 generatedβ-cateninconditional activation mice (β-cat(ex3)Agc1CreER) by breedingAgc1-CreERmice withβ-cateninflox(ex3)/+mice. Results of histologic analysis showed the progressive TMJ defects in 3- and 6-month-oldβ-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 ofβ-cat(ex3)Col2CreERmice,β-cat(ex3)Agc1CreERmice showed much severe morphological defects in the superficial layer of TMJ. This may reflect thatAgc1-CreERmice 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 ofβ-cat(ex3)Agc1CreERmice. Results of proliferating cell nuclear antigen (PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage ofβ-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.