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Open AccessArticle

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

Department of Marine Life Science, Jeju National University, Jeju 63243, Korea
Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 47227, Korea
Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Biotooth Regeneration, Kyungpook National University, Daegu 41940, Korea
Marine Bioprocess Co., Ltd., Busan 46048, Korea
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(9), 472;
Received: 29 July 2020 / Revised: 4 September 2020 / Accepted: 16 September 2020 / Published: 18 September 2020
(This article belongs to the Special Issue Marine Organisms for Bone Regeneration - 2020)
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. View Full-Text
Keywords: Crassostrea gigas; growth performance; osteogenesis; IGF-1; GSK-3β; RUNX2 Crassostrea gigas; growth performance; osteogenesis; IGF-1; GSK-3β; RUNX2
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Molagoda, I.M.N.; Jayasingha, J.A.C.C.; Choi, Y.H.; Park, E.K.; Jeon, Y.-J.; Lee, B.-J.; Kim, G.-Y. Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate. Mar. Drugs 2020, 18, 472.

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