Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate.

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.

• Authors: Ilandarage Menu Neelaka Molagoda, Jayasingha Arachchige Chathuranga Chanaka Jayasingha, Yung Hyun Choi, Eui Kyun Park, You-Jin Jeon, Bae-Jin Lee, Gi-Young Kim
• Journal: Marine drugs (Mar Drugs) Vol. 18 Issue 9 (Sep 18 2020) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 32962034 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Glycerophosphates
• Somatomedins
• Tissue Extracts
• Zebrafish Proteins
• igf1 protein, zebrafish
• Insulin-Like Growth Factor I
• Glycogen Synthase Kinase 3 beta
• Calcium
• beta-glycerophosphoric acid

Topics

• 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, metabolism)
• Mice
• Osteogenesis (drug effects)
• Phosphorylation (drug effects)
• Somatomedins (genetics, metabolism)
• Time Factors
• Tissue Extracts (isolation & purification, pharmacology)
• Up-Regulation (drug effects)
• Zebrafish
• Zebrafish Proteins (genetics, metabolism)