Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies
Abstract Background The impaired blood supply to the bones is an important pathological feature of steroid-induced osteonecrosis of the femoral head (SIONFH). Danshen is a Chinese herb that shows therapeutic effects on SIONFH, but the effects of one of its major bioactive constituents, Tanshinone I...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-023-03934-y |
| _version_ | 1797789615492431872 |
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| author | Kai Sun Yuman Xue Xin Zhang Xiaodong Li Jun Zhao Xilin Xu Xiaofeng Zhang Fubiao Yang |
| author_facet | Kai Sun Yuman Xue Xin Zhang Xiaodong Li Jun Zhao Xilin Xu Xiaofeng Zhang Fubiao Yang |
| author_sort | Kai Sun |
| collection | DOAJ |
| description | Abstract Background The impaired blood supply to the bones is an important pathological feature of steroid-induced osteonecrosis of the femoral head (SIONFH). Danshen is a Chinese herb that shows therapeutic effects on SIONFH, but the effects of one of its major bioactive constituents, Tanshinone I (TsI), on SIONFH remain unknown. Here, we evaluated the effects of TsI on SIONFH, particularly focusing on its effects on angiogenesis, in in vivo and in vitro research. Methods SIONFH was induced in Sprague–Dawley rats by an intramuscular injection of methylprednisolone (40 mg/kg) in combination with an intraperitoneal injection of lipopolysaccharide (20 μg/kg). Morphological alterations of the femoral head were observed by dual-energy X-ray absorptiometry and HE staining. Western blot, qRT-PCR, and immunohistochemical/immunofluorescence staining were used to determine gene expression. Results TsI (10 mg/kg) alleviated bone loss and rescued the expression of angiogenesis-related molecules (CD31, VWF, VEGF, and VEGFR2) in the femoral heads of SIONFH rats. Notably, TsI rescued the down-regulated expression of SRY-box transcription factor 11 (SOX11) in CD31+ endothelial cells in the femoral heads of SIONFH rats. In vitro studies showed that TsI preserved the dexamethasone-harmed angiogenic property (migration and tube formation) of human umbilical vein cells (EA.hy926), suppressed dexamethasone-induced cell apoptosis, reduced pro-apoptotic proteins (cytosolic cytochrome C, Bax, and caspase 3/9) and increased anti-apoptotic protein Bcl-2, whereas silencing of SOX11 reversed these beneficial effects. Conclusions This study demonstrates that TsI alleviates SIONFH and promotes angiogenesis by regulating SOX11 expression. Our work would provide new evidence for the application of TsI to treat SIONFH. Graphical Abstract |
| first_indexed | 2024-03-13T01:53:11Z |
| format | Article |
| id | doaj.art-1aa755eabcda4f51bff79529a7fc5299 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-03-13T01:53:11Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-1aa755eabcda4f51bff79529a7fc52992023-07-02T11:21:12ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-06-0118111510.1186/s13018-023-03934-yTanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studiesKai Sun0Yuman Xue1Xin Zhang2Xiaodong Li3Jun Zhao4Xilin Xu5Xiaofeng Zhang6Fubiao Yang7The First Department of Orthopedics and Traumatology, First Affiliated Hospital, Heilongjiang University of Chinese MedicineThe Second Department of Rehabilitation, The Second Affiliated Hospital of Heilongjiang University of Chinese MedicineGraduate School, Heilongjiang University of Chinese MedicineThe Third Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese MedicineGraduate School, Heilongjiang University of Chinese MedicineThe Third Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese MedicineTeaching and Research Section of Orthopedics and Traumatology, Heilongjiang University of Chinese MedicinePresident’s Office, The Third Affiliated Hospital, Heilongjiang University of Chinese MedicineAbstract Background The impaired blood supply to the bones is an important pathological feature of steroid-induced osteonecrosis of the femoral head (SIONFH). Danshen is a Chinese herb that shows therapeutic effects on SIONFH, but the effects of one of its major bioactive constituents, Tanshinone I (TsI), on SIONFH remain unknown. Here, we evaluated the effects of TsI on SIONFH, particularly focusing on its effects on angiogenesis, in in vivo and in vitro research. Methods SIONFH was induced in Sprague–Dawley rats by an intramuscular injection of methylprednisolone (40 mg/kg) in combination with an intraperitoneal injection of lipopolysaccharide (20 μg/kg). Morphological alterations of the femoral head were observed by dual-energy X-ray absorptiometry and HE staining. Western blot, qRT-PCR, and immunohistochemical/immunofluorescence staining were used to determine gene expression. Results TsI (10 mg/kg) alleviated bone loss and rescued the expression of angiogenesis-related molecules (CD31, VWF, VEGF, and VEGFR2) in the femoral heads of SIONFH rats. Notably, TsI rescued the down-regulated expression of SRY-box transcription factor 11 (SOX11) in CD31+ endothelial cells in the femoral heads of SIONFH rats. In vitro studies showed that TsI preserved the dexamethasone-harmed angiogenic property (migration and tube formation) of human umbilical vein cells (EA.hy926), suppressed dexamethasone-induced cell apoptosis, reduced pro-apoptotic proteins (cytosolic cytochrome C, Bax, and caspase 3/9) and increased anti-apoptotic protein Bcl-2, whereas silencing of SOX11 reversed these beneficial effects. Conclusions This study demonstrates that TsI alleviates SIONFH and promotes angiogenesis by regulating SOX11 expression. Our work would provide new evidence for the application of TsI to treat SIONFH. Graphical Abstracthttps://doi.org/10.1186/s13018-023-03934-ySteroidOsteonecrosis of the femoral headTanshinone IAngiogenesisSRY-box transcription factor 11 |
| spellingShingle | Kai Sun Yuman Xue Xin Zhang Xiaodong Li Jun Zhao Xilin Xu Xiaofeng Zhang Fubiao Yang Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies Journal of Orthopaedic Surgery and Research Steroid Osteonecrosis of the femoral head Tanshinone I Angiogenesis SRY-box transcription factor 11 |
| title | Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies |
| title_full | Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies |
| title_fullStr | Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies |
| title_full_unstemmed | Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies |
| title_short | Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies |
| title_sort | tanshinone i alleviates steroid induced osteonecrosis of femoral heads and promotes angiogenesis in vivo and in vitro studies |
| topic | Steroid Osteonecrosis of the femoral head Tanshinone I Angiogenesis SRY-box transcription factor 11 |
| url | https://doi.org/10.1186/s13018-023-03934-y |
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