Aging and mechanical loading by occlusal disharmony are critical and etiological factors for the onset of temporomandibular joint disorders (TMDs). Senescence-accelerated mouse prone 3 (SAMP3) is one of the animal models for studying age-related degenerative changes of various tissues and organs. To evaluate the influences of both the aging and/or the mechanical loading induced by occlusal disharmony on the SAMP3 TMJ condyle, histological and immunohistochemical analyses were performed.Fifty-five, 4-week-old SAMP3 mice were divided into two groups as an experimental and control. In the experimental group, the maxillary molars were trimmed out from the occlusal plane, which also served as mechanical force loading on the condylar surface. Then the condyles were removed and proceeded for histological and immunohistochemical analysis. The subchondral bone ossification was also evaluated by micro-focusing computed tomography (micro-CT) analysis.The results indicated that induced occlusal disharmony in an aging background promotes TMD, including osteoarthritis (OA) like disease. OA-like TMJ lesions in the SAMP3 mice, accompanied by mandibular condylar cartilage degradation, were characterized by loss of proteoglycans (PGs) and changes of the localization of the extracellular matrix, such as collagen type I, II and MMP13. Changes in the microarchitecture of the condyle were also caused under OA-like lesion. Disrupted Wnt/ -catenin signaling by means of immunohistochemical analysis of -catenin contributes to this irreversible cartilage tissue damage.The present study indicates that the experimentally induced occlusal disharmony (under the age-related background) promotes the TMJ OA accompanied by the alteration to components of the extracellular matrix, and Wnt/ -catenin signaling disorder contributes to these irreversible cartilage tissue damage.