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Open AccessArticle

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

1
Department of Marine Life Science, Jeju National University, Jeju 63243, Korea
2
Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 47227, Korea
3
Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Biotooth Regeneration, Kyungpook National University, Daegu 41940, Korea
4
Marine Bioprocess Co., Ltd., Busan 46048, Korea
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(9), 472; https://doi.org/10.3390/md18090472
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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