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A bovine lactoferrin-derived peptide induced osteogenesis via regulation of osteoblast proliferation and differentiation

Shi P1Fan F1Chen H2Xu Z2Cheng S3Lu W4Du M5.

J Dairy Sci. 2020 Mar 17. pii: S0022-0302(20)30207-1. doi: 10.3168/jds.2019-17425. [Epub ahead of print]

Abstract

Osteoporosis is a disease of aging, characterized by a decrease in bone quality and a reduction in bone strength. Promoting the activity of osteoblasts is a useful strategy for combating the progression of osteoporosis. As a novel bone growth factor, lactoferrin plays a role in the anabolic activity in bone by inducing the proliferation and differentiation of osteoblasts and inhibiting the formation of osteoclasts. However, potential peptides with osteogenic activity from lactoferrin have not been identified. In the present study, a peptide with osteogenic activity-LFP-C, fragment residues 624 to 632, derived from lactoferrin hydrolysates-was identified using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry and screened using molecular docking analysis. The LFP-C peptide significantly increased the proliferation of mouse cell line MC3T3-E1 and had a promoting effect on alkaline phosphatase activity and calcium deposition. Moreover, LFP-C increased the proportion of osteoblasts in the G2 and M phases. The osteogenic mechanism of LFP-C was also studied by molecular docking. We found that LFP-C could bind to the key domain (Lys13-Thr15-Gln16-Leu17-Gly18-Asp22) of epidermal growth factor receptor, a vital receptor tyrosine kinase that leads to the activation of the mitogen-activated protein kinase pathway. The main interaction forces were interpolated charge, hydrophobicity, and hydrogen bonding. Results indicated that LFP-C may play an osteogenic role in a similar way to lactoferrin, by promoting the proliferation and differentiation of osteoblasts. The findings of this in vitro experiment also demonstrated that the molecular docking method could play a role in the screening process; this in silico approach allowed for faster and cheaper identification of a promising bioactive component.