摘要Osteoporotic treatments have largely depended on antiresorptive or anabolic drugs;but the former also suppresses new bone formation,and the latter only includes human parathyroid hormone.There is no drug that has a dual effect to inhibit bone resorption and to stimulate bone formation simultaneously.Here,we report a small molecule,a quinoxaline derivative of oleanolic acid (QOA-8a) that plays such dual roles in osteoblasts and osteoclasts in the treatment of osteoporosis.Osteoclast differentiation was induced by incubation of primary mouse bone marrow-derived macrophages in the presence of RANKL and M-CSF,treatment with QOA-8a dose-dependently inhibited the osteoclast formation with an IC50 value of 0.098 μmol/L.QOA-8a also directly acted on osteoblasts,and stimulated new bone formation in murine calvarial bones in vitro and in vivo.In an OVX rat model,administration of QOA-8a (1,5 mg· kg-1·d1,po) for 16 weeks effectively prevented OVX-induced bone loss,accompanied by decreased serum levels of the bone resorption marker CTX-1 and increased serum levels of osteoblast marker N-MID-OT.Meaningfully,our preliminary study revealed that QOA-8a down-regulated the ERK1/2 signal in osteoclasts and up-regulated the signal in osteoblasts.QOA-8a showed dual functions in both animal and human osteoclastogenesis and osteoblastogenesis.Our results demonstrate that QOA-8a might serve as a lead compound with a dual function of bone anabolic and anti-resorptive effects in the development of anti-osteoporosis agents.