Cell Proliferation Stimulation Ability and Osteogenic Activity of Low Molecular Weight Peptides Derived from Bovine Gelatin Hydrolysates

Abstract

It has been recognized that collagen peptides of MW 878 Da (CP1) promote osteoblast proliferation and mineralization. The objective of this study is to identify the peptides responsible for proliferation of osteoblast growth, enhancement of ALP (alkaline phosphatase) activity in osteoblasts and promotion of osteoblast mineralization. To this end, the CP1 were fractioned by a series of chromatography procedures, and 51 peptides from the fraction possessing the most powerful cell proliferation ability were identified by LC–MS–MS. The peptides, GPAGPSGPAGK and GPPGSPGPR, were validated on a simultaneous basis as possessing enhanced bioactivity-inducing properties. In particular, the ALP activity of the cells treated with these two peptides was almost twice that of the control cells. Hydrogen bonds were formed, and the hydrophobic interactions with the EGFR (epidermal growth factor receptor) might be responsible for the osteoblast proliferation activity. On this basis, the two peptides might be potential lead compounds against osteoporosis and osteoarthritis.

A Yeast-Derived Peptide Promotes Skin Wound Healing by Stimulating Effects on Fibroblast and Immunomodulatory Activities

“…In agreement with these results, Wang and co-workers also observed a higher cell growth rate after 24 h compared to 48 and 72 h by studying the proliferation effects of peptides from bovine gelatin hydrolysate on MC3T3-E1 cell line, indicating that peptides can stimulate cell growth in a short time [22]. None of the peptides examined showed significant cytotoxicity throughout the study, and the peptides VL-9, VY-9, VW-9, VF-9, VCK-9, VHK-9, VYK-9, SK-7, and YR-10 significantly increased cell growth.…”

Impact of Hydrolyzed Collagen from Defatted Sea Bass Skin on Proliferation and Differentiation of Preosteoblast MC3T3-E1 Cells

“…In general, the size of peptides is a vital factor affecting bioactivity of HC [ 8 ]. Peptides of smaller sizes mostly exhibited higher bioactivities, especially osteoblast proliferation activity [ 9 , 10 ]. In addition, short chain peptides could be rapidly digested and absorbed in the human body [ 11 ].…”

“…The increased proliferation of cells indicated that HC could induce the proliferation of osteoblast cells. Peptides rich in hydrophobic AAs and imino acids might play a vital role in proliferation [ 9 , 12 ]. Moreover, HC rich in Pro-Hyp and Pro-Hyp-Gly have been shown to induce the growth of osteoblast cells [ 12 , 13 ], and a previous work has demonstrated the presence of these peptides in HC from sea bass skin [ 14 ].…”

“…Moreover, HC rich in Pro-Hyp and Pro-Hyp-Gly have been shown to induce the growth of osteoblast cells [ 12 , 13 ], and a previous work has demonstrated the presence of these peptides in HC from sea bass skin [ 14 ]. Apart from peptides containing Pro-Hyp and Pro-Hyp-Gly, low molecular weight peptides (<1 kDa) had the ability to enhance osteoblast proliferation [ 9 , 15 ]. Our previous work showed the presence of low MW peptides (<750 Da) in defatted sea bass skin HC [ 7 ], which may have contributed to stimulation of osteoblast proliferation.…”

“…Additionally, fish HC could be utilized in many foods without the limitation or unacceptability due to cultural and religious restrictions [ 8 ]. In general, collagen is the main constituent of bone extracellular matrix [ 9 ]. Collagen serves as a template and may also initiate and propagate mineralization independent of the matrix vesicles, resulting in bone toughness and bone strength [ 10 ].…”