Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae

• Published in: Acta pharmacologica Sinica Vol. 37; no. 10; pp. 1370 - 1380
• Main Authors: Luo, Shi-ying, Chen, Jing-feng, Zhong, Zhi-guo, Lv, Xiao-hua, Yang, Ya-jun, Zhang, Jing-jing, Cui, Liao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2016; Nature Publishing Group
• Subjects: Animals; Benzofurans - pharmacology; Biomedical and Life Sciences; Biomedicine; Danio rerio; Dexamethasone - toxicity; Glucocorticoids - toxicity; Immunology; Internal Medicine; Medical Microbiology; Original; original-article; Osteogenesis - drug effects; Oxidative Stress - drug effects; Pharmacology/Toxicology; Protective Agents - pharmacology; Vaccine; Zebrafish; glucocorticoid; salvianolic acid B; osteogenesis; zebrafish; polyphenol; osteoporosis; oxidative stress
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2016.62

Aim： Our previous studies show that salvianolic acid B （Sal B） promotes osteoblast differentiation and matrix mineralization. In this study, we evaluated the protective effects of Sal B on the osteogenesis in dexamethasone （Dex）-treated larval zebrafish, and elucidated the underlying mechanisms. Methods： At 3 d post fertilization, wild-type AB zebrafish larvae or bone transgenic tg （sp7：egfp） zebrafish larvae were exposed to Sal B, Dex, or a mixture of Dex＋Sal B for 6 d. Bone mineralization in AB strain larval zebrafish was assessed with alizarin red staining, and osteoblast differentiation in tg （spT：egfp） larval zebrafish was examined with fluorescence scanning. The expression of osteoblast- specific genes in the larvae was detected using qRT-PCR assay. The levels of oxidative stress markers （ROS and MDA） in the larvae were also measured. Results： Exposure to Dex （5-20 pmol/L） dose-dependently decreased the bone mineralization area and integral optical density （IOD） in wild-type AB zebrafish larvae and the osteoblast fluorescence area and IOD in tg （spT：egfp） zebrafish larvae. Exposure to Dex （10 pmol/L） significantly reduced the expression of osteoblast-specific genes, including runx2a, osteocalcin （OC）, alkaline phosphatase （ALP） and osterix （sp7）, and increased the accumulation of ROS and MDA in the larvae. Co-exposure to Sal B （0.2-2 pmol/L） dose- dependently increased the bone mineralization area and IOD in AB zebafish larvae and osteoblast fluorescence in tg （sp7：egfp） zebraflsh larvae. Co-exposure to Sal B （2 pmol/L） significantly attenuated deleterious alterations in bony tissue and oxidative stress in both Dex-treated AB zebafish larvae and tg （spT.＇egfp） zebrafish larvae. Conclusion： Sal B stimulates bone formation and rescues GC-caused inhibition on osteogenesis in larval zebrafish by counteracting oxidative stress and increasing the expression of osteoblast-specific genes. Thus, Sal B may have protective effects on bone loss trigged by GC.