Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway
Abstract This study aimed to investigate the antiosteoporotic effects and regulatory mechanisms of estradiol (E2) and vitamin D. MC3T3-E1 cells were treated with E2, vitamin D, or their combination, followed by a systematic assessment of cell proliferation and osteogenic differentiation capacity acr...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-02808-z |
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| author | Xiaoyan Dai Changcun Liu Wenkai Bi Guiwen Zheng Kuan Lv Zhiming Xia |
| author_facet | Xiaoyan Dai Changcun Liu Wenkai Bi Guiwen Zheng Kuan Lv Zhiming Xia |
| author_sort | Xiaoyan Dai |
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| description | Abstract This study aimed to investigate the antiosteoporotic effects and regulatory mechanisms of estradiol (E2) and vitamin D. MC3T3-E1 cells were treated with E2, vitamin D, or their combination, followed by a systematic assessment of cell proliferation and osteogenic differentiation capacity across the treatment groups. Subsequently, miRNA sequencing was performed to analyze differentially expressed miRNAs between the control and E2&vitamin D groups. The target relationship between miR-351-5p and IRS1 was validated, and the effects of the miR-351-5p/IRS1 axis on osteogenesis and mTOR/NFκB signaling pathway were determined after combination treatment. Additionally, an ovariectomized (OVX) osteoporosis mouse model was established to systematically examine the effects of E2, vitamin D, and their combination on osteoporosis and mTOR/NFκB signaling pathway. E2 and vitamin D synergistically promoted MC3T3-E1 cell proliferation and osteogenic differentiation. miR-351-5p was identified through miRNA sequencing analysis. miR-351-5p was downregulated in MC3T3-E1 cells after E2 and vitamin D combination treatment, and its overexpression partially reversed the effect of the combination treatment on osteogenesis. IRS1 was a target of miR-351-5p. When overexpressed, IRS1 partially mitigated the impact of miR-351-5p overexpression on osteogenesis and mTOR/NFκB signaling pathway under the combination treatment. Furthermore, in vivo experiments demonstrated that E2 and vitamin D could synergistically prevent osteoporosis in OVX mice by inhibiting the mTOR/NFκB signaling pathway. In conclusion, E2 and vitamin D exhibited a synergistic effect in preventing osteoporosis through the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway. E2 and vitamin D combination treatment could be a potential anti-osteoporotic strategy for osteoporosis treatment. |
| format | Article |
| id | doaj-art-6f42a7d333c242aa8c6780b3fa20b174 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-6f42a7d333c242aa8c6780b3fa20b1742025-08-20T03:16:50ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-02808-zEstradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathwayXiaoyan Dai0Changcun Liu1Wenkai Bi2Guiwen Zheng3Kuan Lv4Zhiming Xia5Department of Otolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityAbstract This study aimed to investigate the antiosteoporotic effects and regulatory mechanisms of estradiol (E2) and vitamin D. MC3T3-E1 cells were treated with E2, vitamin D, or their combination, followed by a systematic assessment of cell proliferation and osteogenic differentiation capacity across the treatment groups. Subsequently, miRNA sequencing was performed to analyze differentially expressed miRNAs between the control and E2&vitamin D groups. The target relationship between miR-351-5p and IRS1 was validated, and the effects of the miR-351-5p/IRS1 axis on osteogenesis and mTOR/NFκB signaling pathway were determined after combination treatment. Additionally, an ovariectomized (OVX) osteoporosis mouse model was established to systematically examine the effects of E2, vitamin D, and their combination on osteoporosis and mTOR/NFκB signaling pathway. E2 and vitamin D synergistically promoted MC3T3-E1 cell proliferation and osteogenic differentiation. miR-351-5p was identified through miRNA sequencing analysis. miR-351-5p was downregulated in MC3T3-E1 cells after E2 and vitamin D combination treatment, and its overexpression partially reversed the effect of the combination treatment on osteogenesis. IRS1 was a target of miR-351-5p. When overexpressed, IRS1 partially mitigated the impact of miR-351-5p overexpression on osteogenesis and mTOR/NFκB signaling pathway under the combination treatment. Furthermore, in vivo experiments demonstrated that E2 and vitamin D could synergistically prevent osteoporosis in OVX mice by inhibiting the mTOR/NFκB signaling pathway. In conclusion, E2 and vitamin D exhibited a synergistic effect in preventing osteoporosis through the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway. E2 and vitamin D combination treatment could be a potential anti-osteoporotic strategy for osteoporosis treatment.https://doi.org/10.1038/s41598-025-02808-zOsteoporosisEstradiolVitamin DmiR-351-5pIRS1mTOR/NFκB signaling pathway |
| spellingShingle | Xiaoyan Dai Changcun Liu Wenkai Bi Guiwen Zheng Kuan Lv Zhiming Xia Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway Scientific Reports Osteoporosis Estradiol Vitamin D miR-351-5p IRS1 mTOR/NFκB signaling pathway |
| title | Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway |
| title_full | Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway |
| title_fullStr | Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway |
| title_full_unstemmed | Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway |
| title_short | Estradiol and vitamin D exert a synergistic effect on preventing osteoporosis via the miR-351-5p/IRS1 axis and mTOR/NFκB signaling pathway |
| title_sort | estradiol and vitamin d exert a synergistic effect on preventing osteoporosis via the mir 351 5p irs1 axis and mtor nfκb signaling pathway |
| topic | Osteoporosis Estradiol Vitamin D miR-351-5p IRS1 mTOR/NFκB signaling pathway |
| url | https://doi.org/10.1038/s41598-025-02808-z |
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