title: Recombinant human lactoferrin as a biomaterial for bone tissue engineering: mechanism of antiapoptotic and osteogenic activity.
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.
authors.affiliation: Department of Chemical Materials, and Biomolecular Engineering, Biomedical Engineering, Institute of Material Science, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Amini
authors.forename: Lakshmi S
authors.initials: LS
authors.lastname: Nair
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007781:Lactoferrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D023822:Tissue Engineering; D014439:Tyramine / Q000737:chemistry; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D011994:Recombinant Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D051176:beta Catenin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D017868:Cyclic AMP-Dependent Protein Kinases; D007781:Lactoferrin; D014439:Tyramine
keywords: anti-apoptotic; injectable hydrogels; lactoferrin; ligands; receptor-mediated cell signaling