Department of Chemical Materials, and Biomolecular Engineering, Biomedical Engineering, Institute of Material Science, University of Connecticut, Storrs, CT 06269, USA.
Adv Healthc Mater. 2014 Jun;3(6):897-905. doi: 10.1002/adhm.201300496. Epub 2013 Dec 18.
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.
乳铁蛋白是一种具有独特性质的生物活性球形蛋白，对肌骨细胞具有生物活性，并在体内具有促进骨形成的作用。尽管乳铁蛋白具有很强的抗细胞凋亡和促骨生成活性，但作用机制尚未完全阐明。本研究表明，rhLF 对 MC3T3 前成骨细胞的抗凋亡作用是通过 Wnt5a/PKA 途径介导的，rhLF 稳定 β-catenin 依赖于 PKA/LRP6 信号通路。本研究还探讨了将 rhLF 开发为细胞递送生物材料的可行性。通过在存在过氧化物酶和辣根过氧化物酶的情况下，用酪胺修饰的 rhLF 进行酶交联，制备可注射的 rhLF 细胞递送载体。修饰后的 rhLF 表现出与未修饰 rhLF 相似的生物活性。rhLF 凝胶支持包封的 MC3T3 细胞的活力、增殖和分化，以及信号蛋白的磷酸化。总之，本研究表明 Wnt5a、LRP6 和 PKA 信号通路参与 rhLF 介导的 MC3T3 细胞的生物活性，并证明了从 rhLF 开发可注射细胞递送载体的可行性。
