PUBLICATION
Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate
- Authors
- Molagoda, I.M.N., Jayasingha, J.A.C.C., Choi, Y.H., Park, E.K., Jeon, Y.J., Lee, B.J., Kim, G.Y.
- ID
- ZDB-PUB-201002-127
- Date
- 2020
- Source
- Marine drugs 18(9): (Journal)
- Registered Authors
- Keywords
- Crassostrea gigas, GSK-3β, IGF-1, RUNX2, growth performance, osteogenesis
- MeSH Terms
-
- 3T3 Cells
- Animals
- Calcium/metabolism
- Crassostrea/chemistry*
- Dose-Response Relationship, Drug
- Fermentation
- Gene Knockdown Techniques
- Glycerophosphates/pharmacology
- Glycogen Synthase Kinase 3 beta/metabolism
- Insulin-Like Growth Factor I/genetics
- Insulin-Like Growth Factor I/metabolism
- Mice
- Osteogenesis/drug effects*
- Phosphorylation/drug effects
- Somatomedins/genetics
- Somatomedins/metabolism*
- Time Factors
- Tissue Extracts/isolation & purification
- Tissue Extracts/pharmacology*
- Up-Regulation/drug effects
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 32962034 Full text @ Mar. Drugs
Citation
Molagoda, I.M.N., Jayasingha, J.A.C.C., Choi, Y.H., Park, E.K., Jeon, Y.J., Lee, B.J., Kim, G.Y. (2020) Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate. Marine drugs. 18(9):.
Abstract
Fermented oyster (Crassostrea gigas) extract (FO) prevents ovariectomy-induced osteoporosis by inhibiting osteoclastogenesis and activating osteogenesis. However, the molecular mechanisms underlying FO-mediated bone formation and growth rate are unclear. In the current study, we found that FO significantly upregulated the expression of growth-promoting genes in zebrafish larvae including insulin-like growth factor 1 (zigf-1), insulin-like growth factor binding protein 3 (zigfbp-3), growth hormone-1 (zgh-1), growth hormone receptor-1 (zghr-1), growth hormone receptor alpha (zghra), glucokinase (zgck), and cholecystokinin (zccka). In addition, zebrafish larvae treated with 100 μg/mL FO increased in total body length (3.89 ± 0.13 mm) at 12 days post fertilization (dpf) compared to untreated larvae (3.69 ± 0.02 mm); this effect was comparable to that of the β-glycerophosphate-treated zebrafish larvae (4.00 ± 0.02 mm). Furthermore, FO time- and dose-dependently increased the extracellular release of IGF-1 from preosteoblast MC3T3-E1 cells, which was accompanied by high expression of IGF-1. Pharmacological inhibition of IGF-1 receptor (IGF-1R) using picropodophyllin (PPP) significantly reduced FO-mediated vertebrae formation (from 9.19 ± 0.31 to 5.53 ± 0.35) and growth performance (from 3.91 ± 0.02 to 3.69 ± 0.01 mm) in zebrafish larvae at 9 dpf. Similarly, PPP significantly decreased FO-induced calcium deposition in MC3T3-E1 cells by inhibiting GSK-3β phosphorylation at Ser9. Additionally, DOI hydrochloride, a potent stabilizer of GSK-3β, reduced FO-induced nuclear translocation of RUNX2. Transient knockdown of IGF-1Rα/β using specific silencing RNA also resulted in a significant decrease in calcium deposition and reduction in GSK-3β phosphorylation at Ser9 in MC3T3-E1 cells. Altogether, these results indicate that FO increased phosphorylated GSK-3β at Ser9 by activating the autocrine IGF-1-mediated IGF-1R signaling pathway, thereby promoting osteogenesis and growth performance. Therefore, FO is a potential nutritional supplement for bone formation and growth.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping