Pinoresinol diglucoside mitigates dexamethasone-induced osteoporosis and chondrodysplasia in zebrafish.

Autor: Zuo Y; School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325003, China., Chen C; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China; Department of Epidemiology, School of Public Health and General Medicine, Tongji University, School of Medicine, Shanghai 200092, China., Liu F; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China., Hu H; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China; Department of Epidemiology, School of Public Health and General Medicine, Tongji University, School of Medicine, Shanghai 200092, China., Dong S; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China., Shen Q; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China., Zeng J; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China., Huang L; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China., Liao X; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China., Cao Z; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China., Zhong Z; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China; Department of Epidemiology, School of Public Health and General Medicine, Tongji University, School of Medicine, Shanghai 200092, China., Lu H; Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Ji'an 343009, Jiangxi, China. Electronic address: luhq2@126.com., Chen J; School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325003, China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Pediatrics, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China; Department of Epidemiology, School of Public Health and General Medicine, Tongji University, School of Medicine, Shanghai 200092, China. Electronic address: chenjianjun@tongji.edu.cn.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Mar; Vol. 484, pp. 116884. Date of Electronic Publication: 2024 Mar 03.
DOI: 10.1016/j.taap.2024.116884
Abstrakt: Background: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly.
Objective: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia.
Methods: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors.
Results: PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5.
Conclusion: PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE