Protein Corona of Magnetic Hydroxyapatite Scaffold Improves Cell Proliferation via Activation of Mitogen-Activated Protein Kinase Signaling Pathway.
The beneficial effect of magnetic scaffolds on the improvement of cell proliferation has been well documented. Nevertheless, the underlying mechanisms about the magnetic scaffolds stimulating cell proliferation remain largely unknown. Once the scaffold enters into the biological fluids, a protein corona forms and directly influences the biological function of scaffold. This study aimed at investigating the formation of protein coronas on hydroxyapatite (HA) and magnetic hydroxyapatite (MHA) scaffolds in vitro and in vivo, and consequently its effect on regulating cell proliferation. The results demonstrated that magnetic nanoparticles (MNP)-infiltrated HA scaffolds altered the composition of protein coronas and ultimately contributed to increased concentration of proteins related to calcium ions, G-protein coupled receptors (GPCRs), and MAPK/ERK cascades as compared with pristine HA scaffolds. Noticeably, the enriched functional proteins on MHA samples could efficiently activate of the MAPK/ERK signaling pathway, resulting in promoting MC3T3-E1 cell proliferation, as evidenced by the higher expression levels of the key proteins in the MAPK/ERK signaling pathway, including mitogen-activated protein kinase kinases1/2 (MEK1/2) and extracellular signal regulated kinase 1/2 (ERK1/2). Artificial down-regulation of MEK expression can significantly down-regulate the MAPK/ERK signaling and consequently suppress the cell proliferation on MHA samples. These findings not only provide a critical insight into the molecular mechanism underlying cellular proliferation on magnetic scaffolds, but also have important implications in the design of magnetic scaffolds for bone tissue engineering.
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Yue
Y
Zhu
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Qi
Q
Yang
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Minggang
M
Yang
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Xiaohui
X
Zhan
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Fang
F
Lan
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Jing
J
He
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Zhongwei
0000-0003-1547-6880
Z
Gu
National Engineering Research Center for Biomaterials, Sichuan University , Chengdu, Sichuan 610064, P.R. China.
Yao
0000-0002-0524-4042
Y
Wu
D016475:3T3 Cells; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D017886:Durapatite / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000066970:Protein Corona / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D058185:Magnetite Nanoparticles; D000066970:Protein Corona; D017886:Durapatite; D020928:Mitogen-Activated Protein Kinases
MAPK signaling pathway; cell proliferation; magnetic hydroxyapatite scaffold; magnetic nanoparticles; protein corona; tissue engineering