Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling
Background: Postmenopausal osteoporosis is characterized by osteoclast differentiation and bone loss. Tangeretin (TGN) is a natural product that possesses multiple pharmacological properties. However, its specific function in postmenopausal osteoporosis deserves further exploration. Methods: The in...
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Elsevier
2025-12-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320425000951 |
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| author | Tengfei Wu Fang Wang Changqing Ai Li Li Fan Wu |
| author_facet | Tengfei Wu Fang Wang Changqing Ai Li Li Fan Wu |
| author_sort | Tengfei Wu |
| collection | DOAJ |
| description | Background: Postmenopausal osteoporosis is characterized by osteoclast differentiation and bone loss. Tangeretin (TGN) is a natural product that possesses multiple pharmacological properties. However, its specific function in postmenopausal osteoporosis deserves further exploration. Methods: The in vitro and in vivo models of postmenopausal osteoporosis were established by using BMMs stimulated with M-CSF and RANKL and mice receiving ovariectomized (OVX) operation. Osteoclast-specific gene expression was determined by RT-qPCR. The protein level was detected by Western blotting. H&E staining was performed to observe the pathological changes in murine distal femurs. Results: For in vitro study, TGN did not affect cell viability but downregulated RANKL-stimulated osteoclast-specific gene expression. For in vivo study, TGN not only alleviated OVX-triggered pathological alterations of femur tissue, but also effectively inhibited proteoglycan loss and cartilage injury induced by OVX in the femurs of mice. Additionally, TGN prevented osteoclastogenesis in OVX mice by downregulating TRAP activity and osteoclast-specific gene expression. Mechanistically, TGN significantly inhibited the activation of Notch signaling via the downregulation of Notch-1, Notch-2, Notch-3, Jagged1, Hes-1, and Hey-1 protein levels in vitro and in vivo. Conclusion: TGN represses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling. |
| format | Article |
| id | doaj-art-7e6d3f2ea100400db190cfe3f084f2bc |
| institution | Kabale University |
| issn | 2352-3204 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj-art-7e6d3f2ea100400db190cfe3f084f2bc2025-08-20T03:45:44ZengElsevierRegenerative Therapy2352-32042025-12-013013614310.1016/j.reth.2025.04.019Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signalingTengfei Wu0Fang Wang1Changqing Ai2Li Li3Fan Wu4Department of Orthopaedics and Traumatology, Shanghai East Hospital, School of Medicine, Tongji University, No.150 Jimo Road, Pudong New District, Shanghai, ChinaCorresponding author. Shanghai East Hospital, School of Medicine, Tongji University, No.150 Jimo Road, Pudong New District, Shanghai, China.; Department of Orthopaedics and Traumatology, Shanghai East Hospital, School of Medicine, Tongji University, No.150 Jimo Road, Pudong New District, Shanghai, ChinaDepartment of Orthopaedics and Traumatology, Shanghai East Hospital, School of Medicine, Tongji University, No.150 Jimo Road, Pudong New District, Shanghai, ChinaDepartment of Orthopaedics and Traumatology, Shanghai East Hospital, School of Medicine, Tongji University, No.150 Jimo Road, Pudong New District, Shanghai, ChinaDepartment of Orthopaedics and Traumatology, Shanghai East Hospital, School of Medicine, Tongji University, No.150 Jimo Road, Pudong New District, Shanghai, ChinaBackground: Postmenopausal osteoporosis is characterized by osteoclast differentiation and bone loss. Tangeretin (TGN) is a natural product that possesses multiple pharmacological properties. However, its specific function in postmenopausal osteoporosis deserves further exploration. Methods: The in vitro and in vivo models of postmenopausal osteoporosis were established by using BMMs stimulated with M-CSF and RANKL and mice receiving ovariectomized (OVX) operation. Osteoclast-specific gene expression was determined by RT-qPCR. The protein level was detected by Western blotting. H&E staining was performed to observe the pathological changes in murine distal femurs. Results: For in vitro study, TGN did not affect cell viability but downregulated RANKL-stimulated osteoclast-specific gene expression. For in vivo study, TGN not only alleviated OVX-triggered pathological alterations of femur tissue, but also effectively inhibited proteoglycan loss and cartilage injury induced by OVX in the femurs of mice. Additionally, TGN prevented osteoclastogenesis in OVX mice by downregulating TRAP activity and osteoclast-specific gene expression. Mechanistically, TGN significantly inhibited the activation of Notch signaling via the downregulation of Notch-1, Notch-2, Notch-3, Jagged1, Hes-1, and Hey-1 protein levels in vitro and in vivo. Conclusion: TGN represses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling.http://www.sciencedirect.com/science/article/pii/S2352320425000951Postmenopausal osteoporosisTGNOsteoclast differentiationNotch signaling |
| spellingShingle | Tengfei Wu Fang Wang Changqing Ai Li Li Fan Wu Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling Regenerative Therapy Postmenopausal osteoporosis TGN Osteoclast differentiation Notch signaling |
| title | Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling |
| title_full | Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling |
| title_fullStr | Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling |
| title_full_unstemmed | Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling |
| title_short | Tangeretin suppresses RANKL-induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting Notch signaling |
| title_sort | tangeretin suppresses rankl induced osteoclastogenesis and alleviates postmenopausal osteoporosis by inhibiting notch signaling |
| topic | Postmenopausal osteoporosis TGN Osteoclast differentiation Notch signaling |
| url | http://www.sciencedirect.com/science/article/pii/S2352320425000951 |
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