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

Fermented oyster (<i>Crassostrea gigas</i>) 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 f...

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Main 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
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/18/9/472
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spelling doaj-c0725954298543488865b8e1ebc1a5632020-11-25T03:33:11ZengMDPI AGMarine Drugs1660-33972020-09-011847247210.3390/md18090472Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth RateIlandarage Menu Neelaka Molagoda0Jayasingha Arachchige Chathuranga Chanaka Jayasingha1Yung Hyun Choi2Eui Kyun Park3You-Jin Jeon4Bae-Jin Lee5Gi-Young Kim6Department of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan 47227, KoreaDepartment of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Biotooth Regeneration, Kyungpook National University, Daegu 41940, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaMarine Bioprocess Co., Ltd., Busan 46048, KoreaDepartment of Marine Life Science, Jeju National University, Jeju 63243, KoreaFermented oyster (<i>Crassostrea gigas</i>) 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 (<i>zigf-1</i>), insulin-like growth factor binding protein 3 (<i>zigfbp-3</i>), growth hormone-1 (<i>zgh-1</i>), growth hormone receptor-1 (<i>zghr-1</i>), growth hormone receptor alpha (<i>zghra</i>), glucokinase (<i>zgck</i>), and cholecystokinin (<i>zccka</i>). 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 <i>IGF-1</i>. 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 <i>IGF-1Rα</i>/<i>β</i> 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.https://www.mdpi.com/1660-3397/18/9/472<i>Crassostrea gigas</i>growth performanceosteogenesisIGF-1GSK-3βRUNX2
collection DOAJ
language English
format Article
sources DOAJ
author Ilandarage Menu Neelaka Molagoda
Jayasingha Arachchige Chathuranga Chanaka Jayasingha
Yung Hyun Choi
Eui Kyun Park
You-Jin Jeon
Bae-Jin Lee
Gi-Young Kim
spellingShingle Ilandarage Menu Neelaka Molagoda
Jayasingha Arachchige Chathuranga Chanaka Jayasingha
Yung Hyun Choi
Eui Kyun Park
You-Jin Jeon
Bae-Jin Lee
Gi-Young Kim
Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate
Marine Drugs
<i>Crassostrea gigas</i>
growth performance
osteogenesis
IGF-1
GSK-3β
RUNX2
author_facet Ilandarage Menu Neelaka Molagoda
Jayasingha Arachchige Chathuranga Chanaka Jayasingha
Yung Hyun Choi
Eui Kyun Park
You-Jin Jeon
Bae-Jin Lee
Gi-Young Kim
author_sort Ilandarage Menu Neelaka Molagoda
title Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate
title_short Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate
title_full Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate
title_fullStr Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate
title_full_unstemmed Fermented Oyster Extract Promotes Insulin-Like Growth Factor-1-Mediated Osteogenesis and Growth Rate
title_sort fermented oyster extract promotes insulin-like growth factor-1-mediated osteogenesis and growth rate
publisher MDPI AG
series Marine Drugs
issn 1660-3397
publishDate 2020-09-01
description Fermented oyster (<i>Crassostrea gigas</i>) 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 (<i>zigf-1</i>), insulin-like growth factor binding protein 3 (<i>zigfbp-3</i>), growth hormone-1 (<i>zgh-1</i>), growth hormone receptor-1 (<i>zghr-1</i>), growth hormone receptor alpha (<i>zghra</i>), glucokinase (<i>zgck</i>), and cholecystokinin (<i>zccka</i>). 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 <i>IGF-1</i>. 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 <i>IGF-1Rα</i>/<i>β</i> 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.
topic <i>Crassostrea gigas</i>
growth performance
osteogenesis
IGF-1
GSK-3β
RUNX2
url https://www.mdpi.com/1660-3397/18/9/472
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