The role of the PI3K/Akt pathway in adenosine’s mechanism of action in osteoporosis with oxidative stress: A wet-dry experimental approach strategy

Adenosine, a nucleoside, regulates various systems, such as the cardiovascular, immune, and nervous systems, by binding to Adenosine receptors. To elucidate the role of Adenosine in Osteoporosis, this study employed an experimental approach involving the stimulation of bone formation in osteoporotic zebrafish and the reduction of reactive oxygen levels in a glucocorticoid-induced zebrafish model of Osteoporosis with oxidative stress. Adenosine significantly promoted the proliferation of MC3T3-E1 cells and increased the activity of alkaline phosphatase (ALP). It also elevated nitric oxide, glutathione, and superoxide dismutase levels while decreasing malondialdehyde. The target of Adenosine’s impact on Osteoporosis with oxidative stress was elucidated through network pharmacology, revealing the PI3K/Akt pathway, a finding corroborated through RT-qPCR analysis. Hence, we present the mechanism through which Adenosine can be utilized to prevent and manage Osteoporosis accompanied by oxidative stress, distinct from the previously identified mode of action of Adenosine in osteoporosis treatment.