OBJECTIVES: Osteonecrosis of the femoral head(ONFH)is a kind of common disease,which could cause hip dysfunction in middle-aged people.However,there have been no effective treatments for ONFH.Calycosin and cordycepin are main bioactive ingredients of Chinese herb Astragali Radix and cordyceps militaris respectively with varieties of function.The aim of this study was to evaluate the protective effects of calycosin and cordycepin on osteonecrosis of the femoral head.METHODS: In vitro studies were carried out to investigate the effects of calycosin and cordycepin on the inhibition of TLR4/NF-?B signaling pathway and promotion of osteogenic differentiation of bone mesenchymal stem cells.The rat models of glucocorticoid-induced and alcohol-induced ONFH were established.The effects of calycosin and cordycepin on TLR4/NF-?B signaling pathway,osteogenic differentiation and incidences of ONFH in rats were detected.RESULTS:(1)The results of Western blot,qRT-PCR,ELISA and immunofluorescence showed that calycosin could inhibit TLR4/NF-?B signaling pathway in vitro.(2)The results of Western blot,qRT-PCR,Alizarin red staining and ALP staining confirmed that ethanol could inhibit osteogenic differentiation of bone marrow mesenchymal stem cells in vitro and calycosin and cordycepin could promote it.(3)In vivo studies showed that calycosin could significantly inhibit TLR4/NF-?B signaling pathway and cordycepin could promote new bone formation,which contributed to the decreased incidence of ONFH and improved pathological performance.CONCLUSION: Calycosin and cordycepin can prevent and protect ONFH in rats safely and effectively.Its mechanism may be related to the inhibition of TLR4/NF-?B signaling pathway and promotion of osteogenic differentiation of bone marrow mesenchymal stem cells.Calycosin and cordycepin could become potential candidates for pharmaceutic prevention and therapy of the intractable disease. |