Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1
Abstract Background The function of mesenchymal stem cells (MSCs) from patients with osteoporosis (OP) is impaired and worsens in patients with type 2 diabetes mellitus (T2DM). Icariin (ICA) is the major active flavonoid glucoside isolated from traditional Chinese herbal Epimedium pubescens, and con...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-023-03998-w |
| _version_ | 1797778769952374784 |
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| author | Sheng-li Xia Zi-yuan Ma Bin Wang Feng Gao Sheng-yang Guo Xu-han Chen |
| author_facet | Sheng-li Xia Zi-yuan Ma Bin Wang Feng Gao Sheng-yang Guo Xu-han Chen |
| author_sort | Sheng-li Xia |
| collection | DOAJ |
| description | Abstract Background The function of mesenchymal stem cells (MSCs) from patients with osteoporosis (OP) is impaired and worsens in patients with type 2 diabetes mellitus (T2DM). Icariin (ICA) is the major active flavonoid glucoside isolated from traditional Chinese herbal Epimedium pubescens, and confirmed able to improve bone mass of OP patients. Objective To investigate the effect of ICA on the proliferation and osteogenic differentiation of bone-derived MSCs (BMSCs) from patients with OP and T2DM and uncover the potential mechanism. Methods BMSCs were treated with ICA, and proliferation and osteogenic potency were evaluated using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and detection of osteogenic markers (ALP, RUNX2, SPP1, COL1A1, and mineralized nodules) was performed. RNA sequencing and bioinformatic analysis were performed to identify differentially expressed genes (DEGs) after ICA treatment and screen proliferation- and osteogenic differentiation-related processes. Gene gain and loss were performed to confirm the role of the key candidate gene. Results ICA significantly promoted the proliferation and osteogenic differentiation of BMSCs. A total of 173 DEGs were identified after ICA treatment. Six DEGs (GLI-1, IGF2, BMP6, WNT5A, PTHLH, and MAPK14) enriched in both proliferation- and osteogenic differentiation-related processes were screened; GLI-1 had the highest validated |log2FC| value. Overexpression of GLI-1 enhanced the proliferation and osteogenic differentiation of BMSCs, and knockdown of GLI-1 weakened the positive effect of ICA on BMSCs. Conclusion ICA promoted the proliferation and osteogenic differentiation of impaired BMSCs by upregulating GLI-1. |
| first_indexed | 2024-03-12T23:22:19Z |
| format | Article |
| id | doaj.art-767e65cdb63b4da5b3bba0629ab08b2f |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-03-12T23:22:19Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-767e65cdb63b4da5b3bba0629ab08b2f2023-07-16T11:23:00ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-07-0118111210.1186/s13018-023-03998-wIcariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1Sheng-li Xia0Zi-yuan Ma1Bin Wang2Feng Gao3Sheng-yang Guo4Xu-han Chen5Department of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalDepartment of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu HospitalZhoupu Community Health Service CenterAbstract Background The function of mesenchymal stem cells (MSCs) from patients with osteoporosis (OP) is impaired and worsens in patients with type 2 diabetes mellitus (T2DM). Icariin (ICA) is the major active flavonoid glucoside isolated from traditional Chinese herbal Epimedium pubescens, and confirmed able to improve bone mass of OP patients. Objective To investigate the effect of ICA on the proliferation and osteogenic differentiation of bone-derived MSCs (BMSCs) from patients with OP and T2DM and uncover the potential mechanism. Methods BMSCs were treated with ICA, and proliferation and osteogenic potency were evaluated using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and detection of osteogenic markers (ALP, RUNX2, SPP1, COL1A1, and mineralized nodules) was performed. RNA sequencing and bioinformatic analysis were performed to identify differentially expressed genes (DEGs) after ICA treatment and screen proliferation- and osteogenic differentiation-related processes. Gene gain and loss were performed to confirm the role of the key candidate gene. Results ICA significantly promoted the proliferation and osteogenic differentiation of BMSCs. A total of 173 DEGs were identified after ICA treatment. Six DEGs (GLI-1, IGF2, BMP6, WNT5A, PTHLH, and MAPK14) enriched in both proliferation- and osteogenic differentiation-related processes were screened; GLI-1 had the highest validated |log2FC| value. Overexpression of GLI-1 enhanced the proliferation and osteogenic differentiation of BMSCs, and knockdown of GLI-1 weakened the positive effect of ICA on BMSCs. Conclusion ICA promoted the proliferation and osteogenic differentiation of impaired BMSCs by upregulating GLI-1.https://doi.org/10.1186/s13018-023-03998-wIcariinT2DMGLI-1Osteogenic differentiationOsteoporosis |
| spellingShingle | Sheng-li Xia Zi-yuan Ma Bin Wang Feng Gao Sheng-yang Guo Xu-han Chen Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1 Journal of Orthopaedic Surgery and Research Icariin T2DM GLI-1 Osteogenic differentiation Osteoporosis |
| title | Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1 |
| title_full | Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1 |
| title_fullStr | Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1 |
| title_full_unstemmed | Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1 |
| title_short | Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1 |
| title_sort | icariin promotes the proliferation and osteogenic differentiation of bone derived mesenchymal stem cells in patients with osteoporosis and t2dm by upregulating gli 1 |
| topic | Icariin T2DM GLI-1 Osteogenic differentiation Osteoporosis |
| url | https://doi.org/10.1186/s13018-023-03998-w |
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