2. Academic Validation
  3. Viridicatol from the Deep-Sea-Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway

Viridicatol from the Deep-Sea-Derived Fungus Alleviates Bone Loss by Targeting the Wnt/SHN3 Pathway

  • Adv Sci (Weinh). 2025 Jun;12(21):e2416140. doi: 10.1002/advs.202416140.
Chun-Lan Xie 1 2 3,  Shang-Hui Ye 2,  Yu-Ting Yue 2,  Bao-Hong Shi 2,  Jing-Ping Xu 2,  Lian-Jie Li 2,  Zheng-Biao Zou 1,  Matthew B Greenblatt 4 5,  Na Li 2 3 6,  Xian-Wen Yang 1,  Ren Xu 2 3
Affiliations

Affiliations

  • 1 Key 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, China.
  • 2 Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, 361102, China.
  • 3 The First Affiliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal Stem Cells, State Key Laboratory of Cellular Stress Biology, Faculty of Medicine and Life Sciences, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, 361102, China.
  • 4 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.
  • 5 Research Division, Hospital for Special Surgery, New York, NY, 10065, USA.
  • 6 Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.
PMID: 40192033 DOI: 10.1002/advs.202416140
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.

Keywords

Schnurri‐3; bone loss; bone‐targeting nanovesicles; osteoblasts; viridicatol.

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