%0 Journal Article %T Dual roles of QOA-8a in antiosteoporosis: a combination of bone anabolic and anti-resorptive effects %A WU Jing %A SHEN Qi %A CUI Wei %A ZHAO Yu %A HUAI Yue %A ZHANG Yu-chao %A BAO Bei-hua %A LIU Chen-xi %A JIANG Qing %A LI Jian-xin %J Acta Pharmacologica Sinica %D 2018 %B 2018 %9 %! Dual roles of QOA-8a in antiosteoporosis: a combination of bone anabolic and anti-resorptive effects %K %X Abstract 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 IC 50 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 ·d -1 , 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. %U http://www.chinaphar.com/article/view/9722 %V 39 %N 2 %P 230-242 %@ 1745-7254