title: Curcumin improves bone microarchitecture in glucocorticoid-induced secondary osteoporosis mice through the activation of microRNA-365 via regulating MMP-9.
abstract: The present study aimed to investigate bone microarchitecture of the proximal tibia in glucocorticoid-induced osteoporosis (GIOP) mice, and the underlying molecular mechanisms of curcumin in DXM-induced osteoporosis were performed. DXM-treated facilitated to induce hypercalciuria in mice, and curcumin-treated showed a decrease in urine calcium. Curcumin reversed DXM-induced bone resorption, including an increase in serum OCN and a decrease in bone resorption markers CTX and TRAP-5b. H&E staining showed the increased disconnections and separation in trabecular bone network as well as the reduction of trabecular thickness throughout the proximal metaphysis of tibia in GIOP group. Importantly, curcumin reversed DXM-induced trabecular deleterious effects and stimulated bone remodeling. The further evidence showed that curcumin supplement significantly decreased the TRAP-positive stained area and inhibited the activity of OPG/RANKL/RANK signaling in the GIOP mice. Moreover, bioinformatics analysis suggested that miR-365 was a regulator of MMP9. The levels of miR-365 were markedly suppressed; however, curcumin treatment could reverse the downregulation of miR-365 in the tibia of GIOP mice. Simultaneously, the results demonstrated that the mRNA and protein expression of MMP-9 were significantly increased in GIOP mice compared with that of the control group. Curcumin treatment could suppress the expression of MMP-9 in the tibia of GIOP mice. The present study demonstrated the protective effects of curcumin against bone deteriorations in the experimentally DIOP mice, and the underlying mechanism was mediated, at least partially, through the activation of microRNA-365 via suppressing MMP9.
authors.affiliation: Department of Orthopaedics II, Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of General Surgery I, Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, China.
authors.forename: Juyuan
authors.initials: J
authors.lastname: Bu
authors.affiliation: Department of Anesthesiology, Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, China.
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Oral and Maxillofacial Surgery, Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, China.
authors.forename: Zibin
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Orthopaedics II, Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, China.
authors.forename: Rongkai
authors.initials: R
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D019295:Computational Biology; D003474:Curcumin / Q000494:pharmacology*; D003907:Dexamethasone; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D000067996:RAW 264.7 Cells; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000201:enzymology; D014162:Transfection; D055114:X-Ray Microtomography
chemical_list: D020413:3' Untranslated Regions; D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; C000589043:MIRN365 microRNA, mouse; D035683:MicroRNAs; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D003474:Curcumin
keywords: MMP9; Osteoporosis; curcumin; dexamethasone; miR-365