Melatonin prevents bone loss in osteoporotic rats with valproic acid treatment by anti-inflammatory and anti-oxidative stress

Melatonin (MEL) has shown positive effects in anti-inflammatory and anti-oxidative stress research. This study investigates whether MEL can positively impact bone loss induced by valproic acid (VPA) in rats. The study examines changes in MC3T3-E1 cell viability and osteogenic potential, along with osteoclast differentiation in RAW264.7 cells in the presence of VPA using CCK-8, ALP staining, AR staining, and TRAP staining. In vitro experiments reveal that VPA-induced inhibition of osteogenic differentiation and promotion of osteoclastic differentiation are linked to increased inflammation and oxidative stress. Furthermore, MEL has demonstrated the ability to reduce oxidative stress and inflammation, boost osteogenic differentiation, and inhibit osteoclast differentiation. Animal experiments confirm that MEL significantly increases SOD2 expression and decreases TNF-α expression, leading to the restoration of impaired bone metabolism, enhanced bone strength, and higher bone mineral density. The combined experimental results strongly suggest that MEL can enhance osteogenic activity in the presence of VPA by reducing inflammation and oxidative stress, impeding osteoclast differentiation, and alleviating bone loss in VPA-treated rat models.