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

beta-Catenin plays a critical role in cartilage formation and development. To further understand the role of beta-catenin in osteoarthritis (OA) development in temporomandibular joint (TMJ), we have generated beta-catenin conditional activation mice (beta-cat(ex3)(Agc1CreER)) by breeding Agc1-CreER mice with beta-catenin(flox(ex3)/+) mice. Results of histologic analysis showed the progressive TMJ defects in 3- and 6-month-old beta-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 beta-cat(ex3)(Col2CreER) mice, beta-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 beta-cat(ex3)(Agc1CreER) mice. 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 of beta-cat(ex3)(Agc1CreER) mice. Our findings indicate that abnormal upregulation of beta-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that beta-catenin plays a critical role in TMJ pathogenesis.