Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice
Theaflavin-3, 3′-digallate (TF3) is extracted from black tea and has strong antioxidant capabilities. The aim of this study was to assess the influences of TF3 on osteoclastogenesis and explore the underlying mechanisms. TF3 efficiently decreased receptor activator of nuclear factor-kappa B ligand (...
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00803/full |
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| author | Zexin Ai Yang’ou Wu Miao Yu Jia Li Shengjiao Li |
| author_facet | Zexin Ai Yang’ou Wu Miao Yu Jia Li Shengjiao Li |
| author_sort | Zexin Ai |
| collection | DOAJ |
| description | Theaflavin-3, 3′-digallate (TF3) is extracted from black tea and has strong antioxidant capabilities. The aim of this study was to assess the influences of TF3 on osteoclastogenesis and explore the underlying mechanisms. TF3 efficiently decreased receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and reactive oxygen species (ROS) generation in a dose-dependent manner. Mechanistically, TF3 reduced ROS generation by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1) and also inhibited the mitogen-activated protein kinases (MAPK) pathway. Moreover, micro-computed tomography (CT) analysis, hematoxylin and eosin (H&E) staining, and TRAP staining of the femurs of C57BL/6J female mice showed that TF3 markedly attenuated bone loss and osteoclastogenesis in mice. Immunofluorescence staining, 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining, and measurement of the levels of malonaldehyde (MDA) and superoxide dismutase (SOD) revealed that TF3 increased the expression of Nrf2 and decreased the intracellular ROS level in vivo. These findings indicated that TF3 may have the potential to treat osteoporosis and bone diseases related to excessive osteoclastogenesis via inhibiting the intracellular ROS level. |
| first_indexed | 2024-12-13T00:10:03Z |
| format | Article |
| id | doaj.art-d8225d5c63624eefb48826768d1d3408 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T00:10:03Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d8225d5c63624eefb48826768d1d34082022-12-22T00:06:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-06-011110.3389/fphar.2020.00803522453Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in MiceZexin Ai0Yang’ou Wu1Miao Yu2Jia Li3Shengjiao Li4Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Prosthodontics, School and Hospital of Stomatology, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai, ChinaTheaflavin-3, 3′-digallate (TF3) is extracted from black tea and has strong antioxidant capabilities. The aim of this study was to assess the influences of TF3 on osteoclastogenesis and explore the underlying mechanisms. TF3 efficiently decreased receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and reactive oxygen species (ROS) generation in a dose-dependent manner. Mechanistically, TF3 reduced ROS generation by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1) and also inhibited the mitogen-activated protein kinases (MAPK) pathway. Moreover, micro-computed tomography (CT) analysis, hematoxylin and eosin (H&E) staining, and TRAP staining of the femurs of C57BL/6J female mice showed that TF3 markedly attenuated bone loss and osteoclastogenesis in mice. Immunofluorescence staining, 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining, and measurement of the levels of malonaldehyde (MDA) and superoxide dismutase (SOD) revealed that TF3 increased the expression of Nrf2 and decreased the intracellular ROS level in vivo. These findings indicated that TF3 may have the potential to treat osteoporosis and bone diseases related to excessive osteoclastogenesis via inhibiting the intracellular ROS level.https://www.frontiersin.org/article/10.3389/fphar.2020.00803/fulltheaflavin-3,3′-digallateosteoclastreactive oxygen speciesNrf2osteoporosis |
| spellingShingle | Zexin Ai Yang’ou Wu Miao Yu Jia Li Shengjiao Li Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice Frontiers in Pharmacology theaflavin-3,3′-digallate osteoclast reactive oxygen species Nrf2 osteoporosis |
| title | Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice |
| title_full | Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice |
| title_fullStr | Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice |
| title_full_unstemmed | Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice |
| title_short | Theaflavin-3, 3′-Digallate Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Ovariectomy-Induced Bone Loss in Mice |
| title_sort | theaflavin 3 3 digallate suppresses rankl induced osteoclastogenesis and attenuates ovariectomy induced bone loss in mice |
| topic | theaflavin-3,3′-digallate osteoclast reactive oxygen species Nrf2 osteoporosis |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00803/full |
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