| Background and objective:Postmenopausal osteoporosis,which increases the risk of fracture,is the most common bone disease in women.Postmenopausal osteoporosis not only increases the risk of death but also imposes a financial burden on countless families.At present,most of the drugs used to treat osteoporosis have significant side effects,so it is important to find effective anti-osteoporosis medications without major side effects.In recent years,more and more Chinese herbal medicine monomers with Chinese characteristics-lignans have been used in the treatment of anti-osteoporosis drugs,and most of these Chinese herbal medicine monomers of lignans are natural extracts.They not only have a variety of pharmacological effects such as anti-oxidation,anti-cancer,anti-tumor,but also have good effects and economic benefits.Numerous advantages make it gradually become one of the hotspots in the research of new anti-osteoporosis drugs.Sesamolin is a natural lignan extracted from sesame seeds.Many researches have shown that Sesamolin has anti-oxidation,anti-cancer,anti-tumor,and nerve protection effects,which similar to most lignan-like Chinese herbal medicine monomers,however it is still unknown whether it has any effect on postmenopausal osteoporosis.We conducted a preliminary exploration to ascertain effects of compounds on osteoclastogenesis,and we found that Sesamolin can indeed inhibit the differentiation of osteoclasts in vitro.In order to further explore the role of Sesamolin in the process of osteoclast differentiation and the osteoporosis model induced by ovariectomized mice,we conducted in vitro and in vivo experiments to find evidence that Sesamolin may be an effective anti-osteoporotic drug candidate without side effects.Methods:1.In vitro experiments:(1)We used TRAc P staining,podosomal actin belt immunofluorescence and hydroxyapatite resorption test to detect the effect of Sesamolin on osteoclast formation and bone resorption;(2)Several genes specifically expressed in osteoclasts were determined by RT-PCR;(3)Western blotting analysis of NF-κB and MAPK signal pathways,as well as the expression of c-Fos and NFATc1 two main transcription factors were used to determine the effect of Sesamolin on related signal pathways in the process of osteoclast formation.2.In vivo experiments: we used the osteoporosis model induced in ovariectomized mice to verify the therapeutic effect of Sesamolin;(1)Through HE staining of the heart,liver,spleen and kidney,we explored evaluated the possible toxic effects of Sesamolin in ovariectomized mice;(2)Several genes specifically expressed in osteoclasts were determined by RT-PCR to explore the effect of Sesamolin on the genes specifically expressed in osteoclasts in vivo;(3)Through Micro-CT analysis and histological analysis of femoral slices(histological analysis mainly including HE staining,TRAc P staining,Ctsk and OCN immunohistochemical analysis)to explore the effect of Sesamolin on the osteoporosis induced by ovariectomized mice.Results:1.At the cellular level,we found that Sesamolin can effectively inhibit the formation of osteoclasts and bone resorption in vitro;2.At the protein level,we found that Sesamolin not only effectively inhibits RANKL-induced MAPK and NF-κB signal transduction in vitro,but also attenuate the expression of the two main transcription factors c-Fos and NFATc1;3.At the genetic level,we found that Sesamolin can inhibit the expression of specific genes related to osteoclasts in vivo and in vitro.4.In addition,in vivo,our research also found that Sesamolin can effectively reduce bone loss in ovariectomized mice,and compared with the sham group,the experimental groups showed no significant adverse effects on the heart,liver,spleen or kidney.Conclusion:In this study,we reported for the first time that Sesamolin can protect the bone loss caused by the osteoporosis model induced by ovariectomized mice.This may be closely related to the fact that Sesamolin can inhibit the activation of MAPK and NF-κB signal transduction pathways in vitro,thereby weakening the expression of c-Fos and NFATc1 transcription factors.In conclusion,these results provide promising evidence for Sesamolin as a candidate medication for the treatment of postmenopausal osteoporosis. |
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