Anti-Osteoporotic Effects of Antioxidant Peptides PIISVYWK and FSVVPSPK from Mytilus edulis on Ovariectomized Mice.

Yunok Oh,Won Ho Cho,Chang-Bum Ahn,Na Young Yoon,Jae-Young Je

doi:10.3390/antiox9090866

Abstract

Numerous amounts of evidence suggest that bioactive peptides with diverse physiological activities can be nutraceuticals or potential drug candidates. In this study, blue mussel-derived antioxidant peptides PIISVYWK and FSVVPSPK were subjected to evaluate their osteogenic effect in mouse bone marrow mesenchymal stem cells (mBMMSCs) followed by an in vivo anti-osteoporotic effect. Treatment of PIISVYWK and FSVVPSPK on mBMMSCs stimulated alkaline phosphatase activity and calcification. Western blot results revealed that PIISVYWK and FSVVPSPK increased the expression of bone morphogenetic protein-2/4 (BMP-2/4) followed by upregulating p-Smad1/5, type I collagen, and transcription factors including Runx2 and osterix in mBMMSCs. Two peptides also activated the phosphorylation of MAPKs (p-p38, p-ERK, and p-JNK). Treatment of MAPK inhibitors significantly inhibited the BMP signaling pathway, indicating that PIISVYWK and FSVVPSPK stimulated osteoblast differentiation of mBMMSCs through the MAPK-dependent BMP signaling pathway. The anti-osteoporotic effect of PIISVYWK and FSVVPSPK in ovariectomized (OVX) mice was investigated. Treatment of PIISVYWK and FSVVPSPK for ten weeks showed a notable anti-osteoporotic effect in OVX mice via increasing bone mineral density and other bone parameters compared to OVX mice without peptides. Serum analysis also showed that treatment of PIISVYWK and FSVVPSPK completely reduced osteocalcin and ALP (alkAline phosphatase) activity. Taken together, these results suggest that PIISVYWK and FSVVPSPK could be health-promoting functional food ingredients against osteoporosis.

Highlights

There is a growing interest in the development of bioactive peptides (BAPs) with a potential application as an ingredient of functional foods and nutraceuticals as well as pharmaceuticals.Numerous amounts of evidence and awareness of health-promoting effects of BAPs have been accelerated to develop BAPs from food proteins by enzymatic hydrolysis, which is a well-known approach to produce BAPs without altering nutritional values
Since antioxidant peptides showed multifunctional bioactivity, in this study, as a part of our ongoing investigation on development of bone health-promoting biomaterials, we evaluated the osteogenic effect of two antioxidant peptides on mouse bone marrow mesenchymal stem cells (mBMMSCs)
To investigate the osteogenic effect of PIISVYWK and FSVVPSPK in mBMMSCs associated with mitogen-activated protein kinase (MAPK) signaling pathways, phosphorylated forms of p38, ERK, and JNK were associated with MAPK signaling pathways, phosphorylated forms of p38, ERK, and JNK were assessed by Western blot analysis

Summary

Introduction

There is a growing interest in the development of bioactive peptides (BAPs) with a potential application as an ingredient of functional foods and nutraceuticals as well as pharmaceuticals. Numerous amounts of evidence and awareness of health-promoting effects of BAPs have been accelerated to develop BAPs from food proteins by enzymatic hydrolysis, which is a well-known approach to produce BAPs without altering nutritional values. BAPs act as nutrients and physiological modulating materials, and until now, antioxidant peptides with multifunctional activities are major BAPs developed from food proteins [1]. BAPs have been reported, and these BAPs have high potential nutraceutical and pharmaceutical values due to their bioactivities, including antioxidant, antimicrobial, antitumor, antihypertensive, and neuroprotective activities [2,3,4,5,6,7,8]. Because antioxidant peptides are likely to possess a broad spectrum of bioactivities, it would be worthy investigating the health-promoting effect of utilizing antioxidant peptides

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