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Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats
BACKGROUND: Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478381/ https://www.ncbi.nlm.nih.gov/pubmed/34224402 http://dx.doi.org/10.1097/CM9.0000000000001530 |
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author | Zhang, Yue-Lei Zhu, Zhen-Zhong Zhang, Le-Cheng Wang, Gang |
author_facet | Zhang, Yue-Lei Zhu, Zhen-Zhong Zhang, Le-Cheng Wang, Gang |
author_sort | Zhang, Yue-Lei |
collection | PubMed |
description | BACKGROUND: Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH). METHODS: A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I. RESULTS: Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm(3)vs. 0.0811 mm(3), P < 0.05), shown by micro-CT-based angiography. Furthermore, histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP + Li group compared with the MP group. The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP + Li group than that in the MP group. CONCLUSIONS: We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration. |
format | Online Article Text |
id | pubmed-8478381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-84783812021-09-30 Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats Zhang, Yue-Lei Zhu, Zhen-Zhong Zhang, Le-Cheng Wang, Gang Chin Med J (Engl) Original Articles BACKGROUND: Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH). METHODS: A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I. RESULTS: Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm(3)vs. 0.0811 mm(3), P < 0.05), shown by micro-CT-based angiography. Furthermore, histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP + Li group compared with the MP group. The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP + Li group than that in the MP group. CONCLUSIONS: We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration. Lippincott Williams & Wilkins 2021-09-20 2021-07-01 /pmc/articles/PMC8478381/ /pubmed/34224402 http://dx.doi.org/10.1097/CM9.0000000000001530 Text en Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Original Articles Zhang, Yue-Lei Zhu, Zhen-Zhong Zhang, Le-Cheng Wang, Gang Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats |
title | Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats |
title_full | Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats |
title_fullStr | Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats |
title_full_unstemmed | Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats |
title_short | Lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats |
title_sort | lithium chloride prevents glucocorticoid-induced osteonecrosis of femoral heads and strengthens mesenchymal stem cell activity in rats |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478381/ https://www.ncbi.nlm.nih.gov/pubmed/34224402 http://dx.doi.org/10.1097/CM9.0000000000001530 |
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