Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis
Abstract Background Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis. Methods TargetSc...
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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/s13018-023-03883-6 |
| _version_ | 1797784492416434176 |
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| author | Changxin Wang Jianfei Shen Wei Zhang Xiaoyu Wang Xiaohong Xu Xianghui Lu Dongbin Xu Lan Yao |
| author_facet | Changxin Wang Jianfei Shen Wei Zhang Xiaoyu Wang Xiaohong Xu Xianghui Lu Dongbin Xu Lan Yao |
| author_sort | Changxin Wang |
| collection | DOAJ |
| description | Abstract Background Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis. Methods TargetScan and luciferase reporter assay were applied for verifying the relevance between miR-33a-3p and IGF2. Levels of miR-33a-3p, IGF2, Runx2, ALP and Osterix were checked using RT-qPCR and western blotting. hBMSCs proliferation, apoptosis and ALP activity were analyzed by MTT, flow cytometry (FCM) analysis and ALP detection kit, respectively. Moreover, the calcification of cells was assessed using Alizarin Red S staining. The average BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) assay. Results IGF2 was a target of miR-33a-3p. The level of miR-33a-3p was substantially higher and IGF2 expression was memorably lower in the serum of osteoporosis patients than that in healthy volunteers. Our results also pointed out that miR-33a-3p was reduced and IGF2 expression was enhanced during osteogenic differentiation. We concluded that miR-33a-3p negatively regulated the level of IGF2 in hBMSCs. Besides, miR-33a-3p mimic inhibited the osteogenic differentiation of hBMSCs via inhibiting the level of Runx2, ALP and Osterix and decreasing ALP activity. IGF2 plasmid dramatically reversed the influence of miR-33a-3p mimic on IGF2 expression, hBMSCs proliferation and apoptosis, and osteogenic differentiation of hBMSCs. Conclusion miR-33a-3p affected osteogenic differentiation of hBMSCs by targeting IGF2, indicating a potential use of miR-33a-3p as plasma biomarker and therapeutic target for postmenopausal osteoporosis. |
| first_indexed | 2024-03-13T00:40:41Z |
| format | Article |
| id | doaj.art-731f6685369b43e58461153dbc3fa9be |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-03-13T00:40:41Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-731f6685369b43e58461153dbc3fa9be2023-07-09T11:19:34ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-07-0118111010.1186/s13018-023-03883-6Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosisChangxin Wang0Jianfei Shen1Wei Zhang2Xiaoyu Wang3Xiaohong Xu4Xianghui Lu5Dongbin Xu6Lan Yao7Department of Orthopaedics, The Third Affiliated Hospital of Qiqihar Medical UniversityNuclear Medicine Department, The Third Affiliated Hospital of Qiqihar Medical UniversityEndocrine Department, The Third Affiliated Hospital of Qiqihar Medical UniversityNuclear Medicine Department, The Third Affiliated Hospital of Qiqihar Medical UniversityDepartment of Clinical Laboratory, The Third Affiliated Hospital of Qiqihar Medical UniversityDepartment of Gynaecology, The Third Affiliated Hospital of Qiqihar Medical UniversityQiqihar Medical UniversityNuclear Medicine Department, The Third Affiliated Hospital of Qiqihar Medical UniversityAbstract Background Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis. Methods TargetScan and luciferase reporter assay were applied for verifying the relevance between miR-33a-3p and IGF2. Levels of miR-33a-3p, IGF2, Runx2, ALP and Osterix were checked using RT-qPCR and western blotting. hBMSCs proliferation, apoptosis and ALP activity were analyzed by MTT, flow cytometry (FCM) analysis and ALP detection kit, respectively. Moreover, the calcification of cells was assessed using Alizarin Red S staining. The average BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) assay. Results IGF2 was a target of miR-33a-3p. The level of miR-33a-3p was substantially higher and IGF2 expression was memorably lower in the serum of osteoporosis patients than that in healthy volunteers. Our results also pointed out that miR-33a-3p was reduced and IGF2 expression was enhanced during osteogenic differentiation. We concluded that miR-33a-3p negatively regulated the level of IGF2 in hBMSCs. Besides, miR-33a-3p mimic inhibited the osteogenic differentiation of hBMSCs via inhibiting the level of Runx2, ALP and Osterix and decreasing ALP activity. IGF2 plasmid dramatically reversed the influence of miR-33a-3p mimic on IGF2 expression, hBMSCs proliferation and apoptosis, and osteogenic differentiation of hBMSCs. Conclusion miR-33a-3p affected osteogenic differentiation of hBMSCs by targeting IGF2, indicating a potential use of miR-33a-3p as plasma biomarker and therapeutic target for postmenopausal osteoporosis.https://doi.org/10.1186/s13018-023-03883-6Postmenopausal osteoporosishBMSCsmiR-33a-3p/IGF2 axis |
| spellingShingle | Changxin Wang Jianfei Shen Wei Zhang Xiaoyu Wang Xiaohong Xu Xianghui Lu Dongbin Xu Lan Yao Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis Journal of Orthopaedic Surgery and Research Postmenopausal osteoporosis hBMSCs miR-33a-3p/IGF2 axis |
| title | Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis |
| title_full | Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis |
| title_fullStr | Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis |
| title_full_unstemmed | Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis |
| title_short | Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis |
| title_sort | aberrant expression of mir 33a 3p igf2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis |
| topic | Postmenopausal osteoporosis hBMSCs miR-33a-3p/IGF2 axis |
| url | https://doi.org/10.1186/s13018-023-03883-6 |
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