Recombinant human lactoferrin as a biomaterial for bone tissue engineering: mechanism of antiapoptotic and osteogenic activity

Advanced Healthcare Materials
Ashley A Amini, Lakshmi S Nair

Abstract

Lactoferrin is a bioactive globular protein with unique properties towards musculo-skeletal cells and anabolic to bone in vivo. Even though the potent anti-apoptotic and osteogenic activity of lactoferrin has been reported, the mechanism of action has not been fully elucidated. The study demonstrates that the anti-apoptotic effect of rhLF towards MC3T3 pre-osteoblast cells is mediated by Wnt5a/PKA pathway and the stabilization of β-catenin by rhLF is dependent on PKA/LRP6 signaling pathway. The study also investigates the feasibility of developing rhLF as a biomaterial for cell delivery. The injectable rhLF cell delivery vehicles are prepared by enzymatic crosslinking of tyramine-modified rhLF in the presence of hydrogen peroxide and horseradish peroxidase. The modified rhLF shows bioactivity similar to unmodified rhLF. The rhLF gels support encapsulated MC3T3 cell viability, proliferation, and differentiation, as well as phosphorylation of signaling proteins. In conclusion, the study demonstrates the involvement of Wnt5a, LRP6, and PKA signaling in rhLF-mediated bioactivity towards MC3T3 cells and the feasibility of developing an injectable cell delivery vehicle from rhLF.

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Citations

Jul 21, 2015·Colloids and Surfaces. B, Biointerfaces·Ye TianMalcolm Xing
Jun 9, 2016·Proteomics. Clinical Applications·Wieland SchrödlHeidrun Rhode
May 2, 2018·Biomaterials Science·Mehdi KhanmohammadiJafar Ai
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Dec 24, 2015·Biomedical Materials·Fan LeeMotoichi Kurisawa
Jul 2, 2019·Current Medicinal Chemistry·Madalina IcriverziAnca Roseanu
Oct 23, 2019·Materials·Madalina IcriverziAnca Roseanu
Dec 8, 2020·American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics·Li HuangJianwei Chen
Mar 22, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Artem A AntoshinPeter S Timashev

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