Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway
Abstract As an enticing bone anabolic target, short‐term inhibition of Schnurri‐3 (SHN3) resulted in high‐bone mass due to augmented osteoblast activity. However, no studies are conducted to identify natural products targeting SHN3 inhibition. Herein, a screening strategy for the discovery of marine...
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Wiley
2025-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202416140 |
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| author | Chun‐Lan Xie Shang‐Hui Ye Yu‐Ting Yue Bao‐Hong Shi Jing‐Ping Xu Lian‐Jie Li Zheng‐Biao Zou Matthew B. Greenblatt Na Li Xian‐Wen Yang Ren Xu |
| author_facet | Chun‐Lan Xie Shang‐Hui Ye Yu‐Ting Yue Bao‐Hong Shi Jing‐Ping Xu Lian‐Jie Li Zheng‐Biao Zou Matthew B. Greenblatt Na Li Xian‐Wen Yang Ren Xu |
| author_sort | Chun‐Lan Xie |
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| description | Abstract As an enticing bone anabolic target, short‐term inhibition of Schnurri‐3 (SHN3) resulted in high‐bone mass due to augmented osteoblast activity. However, no studies are conducted to identify natural products targeting SHN3 inhibition. Herein, a screening strategy for the discovery of marine compounds that facilitate osteoblast differentiation by targeting SHN3 silencing is presented. One leading quinolinone alkaloid, viridicatol (VDC), isolated from deep‐sea‐derived fungus, vigorously promotes osteogenic differentiation via the Wnt/SHN3 signaling pathway in osteoblasts, thereby preventing osteoporosis while enhancing bone‐fracture healing in a mouse model. Subsequently, the SDSSD (Ser, Asp, Ser, Ser, Asp) is further employed to engineer bone‐targeting nanovesicles (BT‐NVs) for the optimal delivery of VDC to osteoblasts, which mitigates the bone loss observed in a severe osteogenesis imperfecta model. Hence, these results initially uncover a promising marine natural product, VDC, targeting the Wnt/SHN3 pathway for the treatment of bone loss and highlighting its translational potential in clinical applications. |
| format | Article |
| id | doaj-art-b245bbc9e96a4fe0b04031f36dfab4cb |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b245bbc9e96a4fe0b04031f36dfab4cb2025-08-20T02:32:26ZengWileyAdvanced Science2198-38442025-06-011221n/an/a10.1002/advs.202416140Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 PathwayChun‐Lan Xie0Shang‐Hui Ye1Yu‐Ting Yue2Bao‐Hong Shi3Jing‐Ping Xu4Lian‐Jie Li5Zheng‐Biao Zou6Matthew B. Greenblatt7Na Li8Xian‐Wen Yang9Ren Xu10Key Laboratory of Tropical Translational Medicine of Ministry of Education School of Basic Medicine and Life Sciences Hainan Academy of Medical Sciences Hainan Medical University No. 3 Xueyuan Road Haikou Hainan 571199 ChinaFujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 ChinaFujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 ChinaFujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 ChinaFujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 ChinaFujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education School of Basic Medicine and Life Sciences Hainan Academy of Medical Sciences Hainan Medical University No. 3 Xueyuan Road Haikou Hainan 571199 ChinaDepartment of Pathology and Laboratory Medicine Weill Cornell Medicine New York NY 10065 USAFujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 ChinaKey Laboratory of Tropical Translational Medicine of Ministry of Education School of Basic Medicine and Life Sciences Hainan Academy of Medical Sciences Hainan Medical University No. 3 Xueyuan Road Haikou Hainan 571199 ChinaFujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 ChinaAbstract As an enticing bone anabolic target, short‐term inhibition of Schnurri‐3 (SHN3) resulted in high‐bone mass due to augmented osteoblast activity. However, no studies are conducted to identify natural products targeting SHN3 inhibition. Herein, a screening strategy for the discovery of marine compounds that facilitate osteoblast differentiation by targeting SHN3 silencing is presented. One leading quinolinone alkaloid, viridicatol (VDC), isolated from deep‐sea‐derived fungus, vigorously promotes osteogenic differentiation via the Wnt/SHN3 signaling pathway in osteoblasts, thereby preventing osteoporosis while enhancing bone‐fracture healing in a mouse model. Subsequently, the SDSSD (Ser, Asp, Ser, Ser, Asp) is further employed to engineer bone‐targeting nanovesicles (BT‐NVs) for the optimal delivery of VDC to osteoblasts, which mitigates the bone loss observed in a severe osteogenesis imperfecta model. Hence, these results initially uncover a promising marine natural product, VDC, targeting the Wnt/SHN3 pathway for the treatment of bone loss and highlighting its translational potential in clinical applications.https://doi.org/10.1002/advs.202416140bone lossbone‐targeting nanovesiclesosteoblastsSchnurri‐3viridicatol |
| spellingShingle | Chun‐Lan Xie Shang‐Hui Ye Yu‐Ting Yue Bao‐Hong Shi Jing‐Ping Xu Lian‐Jie Li Zheng‐Biao Zou Matthew B. Greenblatt Na Li Xian‐Wen Yang Ren Xu Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway Advanced Science bone loss bone‐targeting nanovesicles osteoblasts Schnurri‐3 viridicatol |
| title | Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway |
| title_full | Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway |
| title_fullStr | Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway |
| title_full_unstemmed | Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway |
| title_short | Viridicatol from the Deep‐Sea‐Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway |
| title_sort | viridicatol from the deep sea derived fungus alleviates bone loss by targeting the wnt shn3 pathway |
| topic | bone loss bone‐targeting nanovesicles osteoblasts Schnurri‐3 viridicatol |
| url | https://doi.org/10.1002/advs.202416140 |
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