Regulation Mechanism Of Nrf2 Signaling Pathway In Zebrafish Osteoporosis Model

As a common disease characterized by bone microstructural destruction and easy fracture,osteoporosis can cause systemic bone pain,decreased physical function,and limited daily activities.Therefore,it has become one of the major epidemics that affect people’s quality of life.There are many side effects and restrictive conditions for the treatment of osteoporosis at present,and more and more studies have found that oxidative stress induced by reactive oxygen species plays an important role in the occurrence of osteoporosis.Therefore,finding new osteoporosis treatment drugs in medicines that can act as oxidation activators has become a new research hotspot.Nrf2 is one of the key transcription factors regulating cell antioxidant response.When the body is affected by toxic substances,Nrf2 activates and regulates downstream antioxidant protein detoxification enzymes,which is a potential target for the treatment of various diseases.Studies have shown that Nrf2,as an antioxidant stress factor,also plays an important role in bone development and metabolism.In order to explore the regulation mechanism of Nrf2 oxidative stress signaling pathway on abnormal bone metabolism and its therapeutic effect on osteoporosis,this study used zebrafish as a model organism to study bone development and oxidative state of the zebrafish embryo in the case of Nrf2 silencing and activation.At the morphological level,the effects of different treatments on the development and maturation of zebrafish bone tissue were studied by alizarin red staining.At the molecular level,the expression of related genes was detected by oxidative stress-related enzyme activity assay and Real-Time PCR assay to explore the mechanism of Nrf2 signaling pathway in simulating microgravity effect and glucocorticoid-induced zebrafish osteoporosis model.The experimental results show that although the simulated microgravity effect and glucocorticoid-induced zebrafish embryonic bone dysplasia have different mechanisms,they can both be regulated by the Nrf2 signaling pathway.Under the activation condition,Nrf2 can reduce the oxidative damage by regulating the expression of downstream phase II detoxification enzyme gene,widely increase the expression of bone development related genes,thereby alleviating the imbalance of bonemetabolism.n the case of Nrf2 knockdown,the embryo is subjected to more severe oxidative damage.The degree of relief of bone metabolism imbalance is less,and the therapeutic effect of Nrf2 activators on abnormal bone metabolism is also reduced.In addition,salvianolic acid B has a significant therapeutic effect on the regulation of Nrf2-mediated glucocorticoid osteoporosis and could be an ideal candidate for the treatment of glucocorticoid osteoporosis.