Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways
Background: Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption. Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities. The study was designed to investigate the role of shik...
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doaj-0836bc124bae4d399c08144091ecf4142021-05-20T07:41:14ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-06-01126110067Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathwaysKai Chen0Zijun Yan1Yiran Wang2Yilin Yang3Mengxi Cai4Chunyou Huang5Bo Li6Mingyuan Yang7Xiaoyi Zhou8Xianzhao Wei9Changwei Yang10Ziqiang Chen11Xiao Zhai12Ming Li13Department of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, ChinaGraduate Management Unit, Shanghai Changhai Hospital, Navy Medical University, Shanghai 200433, ChinaShanghai Changhai Hospital, Navy Medical University, Shanghai 200433, ChinaShanghai Changhai Hospital, Navy Medical University, Shanghai 200433, ChinaGraduate Management Unit, Shanghai Changhai Hospital, Navy Medical University, Shanghai 200433, ChinaGraduate Management Unit, Shanghai Changhai Hospital, Navy Medical University, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, China; Corresponding authors at: Department of Orthopedics, Changhai Hospital of the Second Military Medical University, No 168, Changhai Road, Shanghai, 200433, China.Department of Orthopedics, Changhai Hospital of Navy Medical University, Shanghai 200433, China; Corresponding authors at: Department of Orthopedics, Changhai Hospital of the Second Military Medical University, No 168, Changhai Road, Shanghai, 200433, China.Background: Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption. Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities. The study was designed to investigate the role of shikonin on postmenopausal osteoporosis and explore its underlying mechanisms. Methods: Immunofluorescence staining was performed to evaluate the effects of shikonin on actin ring formation. The expression levels of the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway were determined by Western blot analysis. To determine whether shikonin influences the receptor activator of nuclear factor-κB ligand (RANKL)-induced association between receptor activator of NF-κB (RANK) and tumor necrosis factor receptor associated factor 6 (TRAF6), immunofluorescence staining and immunoprecipitation experiments were performed. During our validation model, histomorphometric examination and micro-computed tomography (CT) were conducted to assess the morphology of osteoporosis. Results: Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo. At the molecular level, Western blot analysis indicated that shikonin inhibited the phosphorylation of inhibitor of NF-κB (IκB), P50, P65, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38. Interaction of TRAF6 and RANK was prevented, and downstream MAPK and NF-κB signaling pathways were downregulated. Conclusion: Osteoclastic bone resorption was reduced in the presence of shikonin in vitro and in vivo. Shikonin is a promising candidate for treatment of postmenopausal osteoporosis.http://www.sciencedirect.com/science/article/pii/S0753332220302584OsteoporosisShikoninOsteoclastogensisTRAF6Osteoclast |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kai Chen Zijun Yan Yiran Wang Yilin Yang Mengxi Cai Chunyou Huang Bo Li Mingyuan Yang Xiaoyi Zhou Xianzhao Wei Changwei Yang Ziqiang Chen Xiao Zhai Ming Li |
spellingShingle |
Kai Chen Zijun Yan Yiran Wang Yilin Yang Mengxi Cai Chunyou Huang Bo Li Mingyuan Yang Xiaoyi Zhou Xianzhao Wei Changwei Yang Ziqiang Chen Xiao Zhai Ming Li Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways Biomedicine & Pharmacotherapy Osteoporosis Shikonin Osteoclastogensis TRAF6 Osteoclast |
author_facet |
Kai Chen Zijun Yan Yiran Wang Yilin Yang Mengxi Cai Chunyou Huang Bo Li Mingyuan Yang Xiaoyi Zhou Xianzhao Wei Changwei Yang Ziqiang Chen Xiao Zhai Ming Li |
author_sort |
Kai Chen |
title |
Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways |
title_short |
Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways |
title_full |
Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways |
title_fullStr |
Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways |
title_full_unstemmed |
Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways |
title_sort |
shikonin mitigates ovariectomy-induced bone loss and rankl-induced osteoclastogenesis via traf6-mediated signaling pathways |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-06-01 |
description |
Background: Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption. Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities. The study was designed to investigate the role of shikonin on postmenopausal osteoporosis and explore its underlying mechanisms. Methods: Immunofluorescence staining was performed to evaluate the effects of shikonin on actin ring formation. The expression levels of the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway were determined by Western blot analysis. To determine whether shikonin influences the receptor activator of nuclear factor-κB ligand (RANKL)-induced association between receptor activator of NF-κB (RANK) and tumor necrosis factor receptor associated factor 6 (TRAF6), immunofluorescence staining and immunoprecipitation experiments were performed. During our validation model, histomorphometric examination and micro-computed tomography (CT) were conducted to assess the morphology of osteoporosis. Results: Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo. At the molecular level, Western blot analysis indicated that shikonin inhibited the phosphorylation of inhibitor of NF-κB (IκB), P50, P65, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38. Interaction of TRAF6 and RANK was prevented, and downstream MAPK and NF-κB signaling pathways were downregulated. Conclusion: Osteoclastic bone resorption was reduced in the presence of shikonin in vitro and in vivo. Shikonin is a promising candidate for treatment of postmenopausal osteoporosis. |
topic |
Osteoporosis Shikonin Osteoclastogensis TRAF6 Osteoclast |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220302584 |
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