Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy
ObjectiveThis study proposes to explore the protective effect of Zuo-Gui-Wan (ZGW) aqueous extract on spinal glucocorticoid-induced osteoporosis (GIOP) in vivo and in vitro, and the underlying mechanisms of ZGW in GIOP and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMS...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.878963/full |
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| author | Gengyang Shen Gengyang Shen Gengyang Shen Qi Shang Qi Shang Zhida Zhang Zhida Zhang Wenhua Zhao Wenhua Zhao Honglin Chen Honglin Chen Ibrayinjan Mijiti Guifeng Chen Guifeng Chen Xiang Yu Xiang Yu Fuyong Yu Fuyong Yu Peng Zhang Peng Zhang Jiahui He Jiahui He Xuelai Zhang Xuelai Zhang Jingjing Tang Jingjing Tang Jianchao Cui Jianchao Cui De Liang De Liang Lingfeng Zeng Hui Ren Hui Ren Xiaobing Jiang Xiaobing Jiang |
| author_facet | Gengyang Shen Gengyang Shen Gengyang Shen Qi Shang Qi Shang Zhida Zhang Zhida Zhang Wenhua Zhao Wenhua Zhao Honglin Chen Honglin Chen Ibrayinjan Mijiti Guifeng Chen Guifeng Chen Xiang Yu Xiang Yu Fuyong Yu Fuyong Yu Peng Zhang Peng Zhang Jiahui He Jiahui He Xuelai Zhang Xuelai Zhang Jingjing Tang Jingjing Tang Jianchao Cui Jianchao Cui De Liang De Liang Lingfeng Zeng Hui Ren Hui Ren Xiaobing Jiang Xiaobing Jiang |
| author_sort | Gengyang Shen |
| collection | DOAJ |
| description | ObjectiveThis study proposes to explore the protective effect of Zuo-Gui-Wan (ZGW) aqueous extract on spinal glucocorticoid-induced osteoporosis (GIOP) in vivo and in vitro, and the underlying mechanisms of ZGW in GIOP and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) were conducted.MethodsIn vivo, SD rats were randomly divided into three groups: control group (CON), dexamethasone (DEXM) group, and ZGW group, which were given vehicle, DEXM injection, and ZGW intragastric administration at the same time. Vertebral bone microarchitecture, biomechanics, histomorphology, serum AKP activity, and the autophagosome of osteoblasts were examined. The mRNA expressions of let-7f, autophagy-associated genes (mTORC1, Beclin-1, ATG12, ATG5, and LC3), Runx2, and CTSK were examined. In vitro, the let-7f overexpression/silencing vector was constructed and transfected to evaluate the osteogenic differentiation of BMSCs. Western blot was employed to detect the expression of autophagy-associated proteins (ULK2, ATG5, ATG12, Beclin-1, LC3).ResultsIn vivo, ZGW promoted the bone quantity, quality, and strength; alleviated histological damage; increased the serum AKP activity; and reduced the autophagosome number in osteoblasts. Moreover, ZGW increased the let-7f, mTORC1, and Runx2 mRNA expressions and reduced the Beclin-1, ATG12, ATG5, LC3, and CTSK mRNA expressions. In vitro, bioinformatics prediction and dual luciferase reporter gene assay verified that let-7f targeted the binding to ULK2 and negatively regulated the ULK2 expression. Furthermore, by let-7f overexpression/silencing, ZGW may promote osteoblast differentiation of BMSCs by regulating let-7f and autophagy as evidenced by Western blot (ULK2, ATG5, ATG12, Beclin-1, LC3).ConclusionsZGW may ameliorate GC-induced spinal osteoporosis by promoting osteoblast differentiation of BMSCs by activation of let-7f and suppression of autophagy. |
| first_indexed | 2024-12-11T23:03:11Z |
| format | Article |
| id | doaj.art-a34b76b2960c49c980803e7e66948a24 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-11T23:03:11Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-a34b76b2960c49c980803e7e66948a242022-12-22T00:47:01ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-05-011310.3389/fendo.2022.878963878963Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and AutophagyGengyang Shen0Gengyang Shen1Gengyang Shen2Qi Shang3Qi Shang4Zhida Zhang5Zhida Zhang6Wenhua Zhao7Wenhua Zhao8Honglin Chen9Honglin Chen10Ibrayinjan Mijiti11Guifeng Chen12Guifeng Chen13Xiang Yu14Xiang Yu15Fuyong Yu16Fuyong Yu17Peng Zhang18Peng Zhang19Jiahui He20Jiahui He21Xuelai Zhang22Xuelai Zhang23Jingjing Tang24Jingjing Tang25Jianchao Cui26Jianchao Cui27De Liang28De Liang29Lingfeng Zeng30Hui Ren31Hui Ren32Xiaobing Jiang33Xiaobing Jiang34Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, Nanshan Hospital, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen Nanshan Hospital of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First People’s Hospital of Kashgar, Kashgar, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Orthopedics, The 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaLingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, ChinaObjectiveThis study proposes to explore the protective effect of Zuo-Gui-Wan (ZGW) aqueous extract on spinal glucocorticoid-induced osteoporosis (GIOP) in vivo and in vitro, and the underlying mechanisms of ZGW in GIOP and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) were conducted.MethodsIn vivo, SD rats were randomly divided into three groups: control group (CON), dexamethasone (DEXM) group, and ZGW group, which were given vehicle, DEXM injection, and ZGW intragastric administration at the same time. Vertebral bone microarchitecture, biomechanics, histomorphology, serum AKP activity, and the autophagosome of osteoblasts were examined. The mRNA expressions of let-7f, autophagy-associated genes (mTORC1, Beclin-1, ATG12, ATG5, and LC3), Runx2, and CTSK were examined. In vitro, the let-7f overexpression/silencing vector was constructed and transfected to evaluate the osteogenic differentiation of BMSCs. Western blot was employed to detect the expression of autophagy-associated proteins (ULK2, ATG5, ATG12, Beclin-1, LC3).ResultsIn vivo, ZGW promoted the bone quantity, quality, and strength; alleviated histological damage; increased the serum AKP activity; and reduced the autophagosome number in osteoblasts. Moreover, ZGW increased the let-7f, mTORC1, and Runx2 mRNA expressions and reduced the Beclin-1, ATG12, ATG5, LC3, and CTSK mRNA expressions. In vitro, bioinformatics prediction and dual luciferase reporter gene assay verified that let-7f targeted the binding to ULK2 and negatively regulated the ULK2 expression. Furthermore, by let-7f overexpression/silencing, ZGW may promote osteoblast differentiation of BMSCs by regulating let-7f and autophagy as evidenced by Western blot (ULK2, ATG5, ATG12, Beclin-1, LC3).ConclusionsZGW may ameliorate GC-induced spinal osteoporosis by promoting osteoblast differentiation of BMSCs by activation of let-7f and suppression of autophagy.https://www.frontiersin.org/articles/10.3389/fendo.2022.878963/fullZGW aqueous extractGIOPlet-7fautophagyChinese medicine |
| spellingShingle | Gengyang Shen Gengyang Shen Gengyang Shen Qi Shang Qi Shang Zhida Zhang Zhida Zhang Wenhua Zhao Wenhua Zhao Honglin Chen Honglin Chen Ibrayinjan Mijiti Guifeng Chen Guifeng Chen Xiang Yu Xiang Yu Fuyong Yu Fuyong Yu Peng Zhang Peng Zhang Jiahui He Jiahui He Xuelai Zhang Xuelai Zhang Jingjing Tang Jingjing Tang Jianchao Cui Jianchao Cui De Liang De Liang Lingfeng Zeng Hui Ren Hui Ren Xiaobing Jiang Xiaobing Jiang Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy Frontiers in Endocrinology ZGW aqueous extract GIOP let-7f autophagy Chinese medicine |
| title | Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy |
| title_full | Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy |
| title_fullStr | Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy |
| title_full_unstemmed | Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy |
| title_short | Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy |
| title_sort | zuo gui wan aqueous extract ameliorates glucocorticoid induced spinal osteoporosis of rats by regulating let 7f and autophagy |
| topic | ZGW aqueous extract GIOP let-7f autophagy Chinese medicine |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.878963/full |
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