Hederagenin Alleviated Ovariectomy-Induced Bone Loss through the Regulation of Innate Immune Signaling in MiceOA
Objectives:Postmenopausal osteoporosis is the most common form of osteoporosis in clinical practice,affecting millions of postmenopausal women worldwide.Postmenopausal osteoporosis demands safe and effective therapies.This study aimed to evaluate the potential of hederagenin(Hed)for treating osteoporosis and to elucidate its underlying mechanisms of action.Methods:The anti-osteoporotic potential of Hed was assessed by investigating its effects on ovariectomy(OVX)-induced bone loss in mice and on receptor activator of NF-kappaB ligand(RANKL)-induced osteoclast differentiation in RAW264.7 cells.Network pharmacology analysis and molecular docking were employed to identify key targets,which were subsequently validated experimentally.Results:In vitro,Hed suppressed osteoclastogenesis by inhibiting the formation of osteoclasts and F-actin rings and by down-regulating osteoclastspecific genes(Atp6v0d2 and Acp5).In vivo,Hed significantly amelioratedOVX-induced bone loss,restoring trabecular bone volume fraction(BV/TV)and trabecular number(Tb.N),while reducing trabecular separation(Tb.Sp).Network pharmacology analysis identified 142 overlapping targets linking Hed to osteoporosis,including tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),and IL-1β,with enrichment in innate immune signaling and osteoclast differentiation.Molecular docking analysis indicated strong binding affinities between Hed and targets such as TNF-α,IL-6,and IL-1β.Experimentally,Hed was found to decrease RANKL,elevate osteoprotegerin(OPG),and suppress intestinalmRNA levels of pro-inflammatory cytokines such as IL-1β,IL-6,IL-17A,and TNF-α.Conclusion:Hed exerts significant anti-osteoporotic effects inOVX-induced osteoporosis through a dualmechanism involving the suppression of both osteoclastogenesis and innate immune signaling pathways.These findings highlighted Hed’s novel role in modulating immune-bone crosstalk,offering a promising strategy for treating osteolytic diseases without estrogenic side effects.
Zhitao Yang;Huanyu Cheng;Xinli Liu;JieLi;Xin Ming;Beibei Li;Luyao Zhang;Chunqing Ma;Yi Jiao;Shenjia Wu;Ibrar Muhammad Khan;Guanghua Xiong;Hongcheng Wang;Yong Liu
First Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaCollege of Life Science,Anhui Agricultural University,Hefei,230036,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,ChinaFirst Affiliated Hospital of Fuyang Normal University,Fuyang Women and Children’s Hospital,School of Biology and Food Engineering,Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation,Fuyang Normal University,Fuyang,236037,China
医药卫生
Hederageninosteoporosisinnate immune signalingosteoclastogenesisnetwork pharmacology
《BIOCELL》 2026 (1)
P.232-247,16
supported by the Scientific Research Project of Anhui ProvincialHealth Commission(Grant No.AHWJ2021b063)National Natural Scientific Foundation of China(Grant No.82160048)Natural Science Foundation Project of Anhui Province(Grant No.2308085MH265)Major Scientific Research Project of Anhui Provincial Department of Education(Grant No.2024AH040205).
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