Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway
Secondary osteoporosis is triggered mostly by glucocorticoid (GC) therapy. Dexamethasone (DEX) was reported to inhibit osteogenic differentiation in zebrafish larvae and MC3T3-E1 cells in prior research. In this research, we primarily examined the protective impacts of epimedin C on the osteogenic i...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.894832/full |
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| author | Yongxiang Xu Shichun Chen Linxuan Huang Weichao Han Yingying Shao Minyi Chen Yusheng Zhang Ruirong He Baocheng Xie |
| author_facet | Yongxiang Xu Shichun Chen Linxuan Huang Weichao Han Yingying Shao Minyi Chen Yusheng Zhang Ruirong He Baocheng Xie |
| author_sort | Yongxiang Xu |
| collection | DOAJ |
| description | Secondary osteoporosis is triggered mostly by glucocorticoid (GC) therapy. Dexamethasone (DEX) was reported to inhibit osteogenic differentiation in zebrafish larvae and MC3T3-E1 cells in prior research. In this research, we primarily examined the protective impacts of epimedin C on the osteogenic inhibition impact of MC3T3-E1 cells and zebrafish larvae mediated by DEX. The findings illustrated no apparent toxicity for MC3T3-E1 cells after administering epimedin C at increasing dosages from 1 to 60 μM and no remarkable proliferation in MC3T3-E1 cells treated using DEX. In MC3T3-E1 cells that had been treated using DEX, we discovered that epimedin C enhanced alkaline phosphatase activities and mineralization. Epimedin C could substantially enhance the protein expression of osterix (OSX), Runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALPL) in MC3T3-E1 cells subjected to DEX treatment. Additionally, epimedin C stimulated PI3K and AKT signaling pathways in MC3T3-E1 cells that had been treated using DEX. Furthermore, in a zebrafish larvae model, epimedin C was shown to enhance bone mineralization in DEX-mediated bone impairment. We also found that epimedin C enhanced ALPL activity and mineralization in MC3T3-E1 cells treated using DEX, which may be reversed by PI3K inhibitor (LY294002). LY294002 can also reverse the protective impact of epimedin C on DEX-mediated bone impairment in zebrafish larval. These findings suggested that epimedin C alleviated the suppressive impact of DEX on the osteogenesis of zebrafish larval and MC3T3-E1 cells via triggering the PI3K and AKT signaling pathways. Epimedin C has significant potential in the development of innovative drugs for the treatment of glucocorticoid-mediated osteoporosis. |
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| id | doaj.art-49e1e377c7dd4e77ae4e3e35c373ec8d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T03:12:44Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-49e1e377c7dd4e77ae4e3e35c373ec8d2022-12-22T01:22:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.894832894832Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling PathwayYongxiang Xu0Shichun Chen1Linxuan Huang2Weichao Han3Yingying Shao4Minyi Chen5Yusheng Zhang6Ruirong He7Baocheng Xie8Department of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDepartment of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDongguan Institute of Clinical Cancer Research, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDepartment of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDepartment of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDepartment of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDepartment of Pharmacy, The First People’s Hospital of Foshan (The Affiliated Foshan Hospital of Sun Yat-Sen University), Foshan, ChinaDepartment of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaDepartment of Pharmacy, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, ChinaSecondary osteoporosis is triggered mostly by glucocorticoid (GC) therapy. Dexamethasone (DEX) was reported to inhibit osteogenic differentiation in zebrafish larvae and MC3T3-E1 cells in prior research. In this research, we primarily examined the protective impacts of epimedin C on the osteogenic inhibition impact of MC3T3-E1 cells and zebrafish larvae mediated by DEX. The findings illustrated no apparent toxicity for MC3T3-E1 cells after administering epimedin C at increasing dosages from 1 to 60 μM and no remarkable proliferation in MC3T3-E1 cells treated using DEX. In MC3T3-E1 cells that had been treated using DEX, we discovered that epimedin C enhanced alkaline phosphatase activities and mineralization. Epimedin C could substantially enhance the protein expression of osterix (OSX), Runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALPL) in MC3T3-E1 cells subjected to DEX treatment. Additionally, epimedin C stimulated PI3K and AKT signaling pathways in MC3T3-E1 cells that had been treated using DEX. Furthermore, in a zebrafish larvae model, epimedin C was shown to enhance bone mineralization in DEX-mediated bone impairment. We also found that epimedin C enhanced ALPL activity and mineralization in MC3T3-E1 cells treated using DEX, which may be reversed by PI3K inhibitor (LY294002). LY294002 can also reverse the protective impact of epimedin C on DEX-mediated bone impairment in zebrafish larval. These findings suggested that epimedin C alleviated the suppressive impact of DEX on the osteogenesis of zebrafish larval and MC3T3-E1 cells via triggering the PI3K and AKT signaling pathways. Epimedin C has significant potential in the development of innovative drugs for the treatment of glucocorticoid-mediated osteoporosis.https://www.frontiersin.org/articles/10.3389/fphar.2022.894832/fullepimedin CPI3Kand AKT signaling pathwaysosteoporosisdexamethasoneosteogenic differentiation |
| spellingShingle | Yongxiang Xu Shichun Chen Linxuan Huang Weichao Han Yingying Shao Minyi Chen Yusheng Zhang Ruirong He Baocheng Xie Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway Frontiers in Pharmacology epimedin C PI3K and AKT signaling pathways osteoporosis dexamethasone osteogenic differentiation |
| title | Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway |
| title_full | Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway |
| title_fullStr | Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway |
| title_full_unstemmed | Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway |
| title_short | Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway |
| title_sort | epimedin c alleviates glucocorticoid induced suppression of osteogenic differentiation by modulating pi3k akt runx2 signaling pathway |
| topic | epimedin C PI3K and AKT signaling pathways osteoporosis dexamethasone osteogenic differentiation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.894832/full |
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