Dexamethasone-Induced Osteoblast Toxicity: Bioenergetics Dysfunction and Oxidative Stress Unmask Apoptotic Pathways

Aim: Dexamethasone (DEX) is a glucocorticoid commonly used to treat autoimmune and non-infectious inflammatory diseases; however, its role in inducing osteoporosis is poorly understood. Materials and Methods: This study investigates the effects of DEX on cell toxicity, secretory functions, mitochondrial bioenergetics, oxidative stress and apoptosis in human osteoblasts. Results: DEX-induced cell toxicity, as evidenced by elevated Lactate Dehydrogenase (LDH) and MTT assays, with an estimated EC50 of approximately 50 μM. The release of “procollagen type I, osteocalcin and alkaline phosphatase” was significantly reduced. Bioenergetic assays revealed that DEX inhibited ATP synthesis, decreased “mitochondrial membrane potential” and impaired the activity of “mitochondrial complexes I and III,” as well as lactate production/oxygen consumption. Additionally, DEX significantly elevated levels of “Reactive Oxygen Species (ROS), Thiobarbituric Acid Reactive Substances (TBARS) and Nuclear factor erythroid 2-related factor 2 (Nrf2) expression” while reducing the antioxidant levels of “catalase, reduced glutathione and superoxide dismutase.” Caspase assays indicated that DEX elevated active caspases-3, -8 and -9. Furthermore, antioxidants, including “reduced glutathione, the caspase-3 inhibitor Z-VAD-FMK and Co-enzyme Q-10,” significantly alleviated DEX-induced cytotoxicity. Conclusion: The present findings suggest that DEX induces osteoblast cytotoxicity via mitochondrial disruption, oxidative stress and apoptosis, with potential mitigation through antioxidant agents.