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Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies
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), o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311706/ https://www.ncbi.nlm.nih.gov/pubmed/37391758 http://dx.doi.org/10.1186/s13018-023-03934-y |
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author | Sun, Kai Xue, Yuman Zhang, Xin Li, Xiaodong Zhao, Jun Xu, Xilin Zhang, Xiaofeng Yang, Fubiao |
author_facet | Sun, Kai Xue, Yuman Zhang, Xin Li, Xiaodong Zhao, Jun Xu, Xilin Zhang, Xiaofeng Yang, Fubiao |
author_sort | Sun, Kai |
collection | PubMed |
description | 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-023-03934-y. |
format | Online Article Text |
id | pubmed-10311706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103117062023-07-01 Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies Sun, Kai Xue, Yuman Zhang, Xin Li, Xiaodong Zhao, Jun Xu, Xilin Zhang, Xiaofeng Yang, Fubiao J Orthop Surg Res Research Article 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-023-03934-y. BioMed Central 2023-06-30 /pmc/articles/PMC10311706/ /pubmed/37391758 http://dx.doi.org/10.1186/s13018-023-03934-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Sun, Kai Xue, Yuman Zhang, Xin Li, Xiaodong Zhao, Jun Xu, Xilin Zhang, Xiaofeng Yang, Fubiao Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies |
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 | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311706/ https://www.ncbi.nlm.nih.gov/pubmed/37391758 http://dx.doi.org/10.1186/s13018-023-03934-y |
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