Chronic Unpredictable Mild Stress Impacts On Chondrocyte Apoptosis And Long-Bone Growth In Adolescent Mice

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Luh Ayu Asri Wijani , Irwanto , Reny I’thosom , Alpha Fardah Athiyyah , Purwo Sri Rejeki , Risa Etika


Chronic psychosocial stress is considered as a risk factor for somatic disorders, as its associated with alteration in the hypothalamic-pituitary-adrenal (HPA) axis caused increased of blood cortisol level and its ability to induce oxidative stress leading to apoptosis. Currently, there are no known reports on the underlying mechanism of the connection between skeletal and mental health. This study, therefore, aims to use models of depression to explore how long bone growth and chondrocyte apoptosis are affected by chronic unpredictable mild stress [1[. Seven-week-old male Mus musculus mice were exposed to chronic unpredictable mild stress (CUMS) for 7 weeks, whereas control mice were non exposed. At the endpoint, epiphyseal growth plate of femur was analyzed using histological and immunohistochemistry, the length of femur was measured using calipers. Compared with controls, exposure to CUMS resulted in approximately twice fold increase Caspase-3 expression presented chondrocyte apoptosis in femur epiphyseal growth plate of stressed mice. This a was associated with oxidative stress activating the intrinsic pathway leading to apoptosis chondrocytes in the growth plate. Furthermore, the length of femur was significantly decreased and the thickness of epiphyseal growth plate were not significantly reduced, suggesting endochondral ossification was interrupted during the long-bone growth process. This is related to protracted activation within the hypothalamic-pituitary-adrenal axis, and consequently, hypercortisolemia. In this stud we conclude that CUMS have negative impacts on bone, increased chondrocyte apoptosis in epiphyseal growth plate and disturb long bone growth in adolescent mice.

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