The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells

Mao Niu,1,* Xianling Feng,2,* Lei Zhou3 1Department of Stomatology, School of Medical Technology and Nursing, Shenzhen Polytechnic, Shenzhen, 518055, China; 2Department of Pathology, School of Medical, Shenzhen University, Shenzhen, 518060, China; 3Center of Oral Implantology, Guangdong Provincial S...

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Autores principales:	Niu M, Feng X, Zhou L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Simvastatin-loaded nanomicelles ERK1/2 pathway Osteogenic effect Dental implant restoration Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e9aa2de7b3824ad8b37789a916fd36c8
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spelling	oai:doaj.org-article:e9aa2de7b3824ad8b37789a916fd36c82021-12-02T02:56:01ZThe role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells1178-2013https://doaj.org/article/e9aa2de7b3824ad8b37789a916fd36c82018-12-01T00:00:00Zhttps://www.dovepress.com/the-role-of-the-erk12-pathway-in-simvastatin-loaded-nanomicelles-and-s-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mao Niu,1,* Xianling Feng,2,* Lei Zhou3 1Department of Stomatology, School of Medical Technology and Nursing, Shenzhen Polytechnic, Shenzhen, 518055, China; 2Department of Pathology, School of Medical, Shenzhen University, Shenzhen, 518060, China; 3Center of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China *These authors contributed equally to this work and should be considered as co-first authors Objectives: The present study aimed to clarify the role of the ERK1/2 pathway in simvastatin (SV)-loaded nanomicelles (SVNs)- and SV-mediated promotion of cell osteogenic differentiation and explore the molecular mechanisms by which SVNs exhibited a greater efficacy in promoting osteogenic differentiation than SV.Materials and methods: SVNs were synthesized using a dialysis method. MG63 cells were treated with 2.5, 0.25, and 0.025 µmol/L of the drug. The optimal drug dosage was determined by examining the proliferative activity and ALP activity of the MG63 cells. Subsequently, Western blot analysis was performed to analyze the levels of the phosphorylated ERK1/2 proteins in each experimental group at various time points. Finally, the inhibitor PD98059 was used to effectively inhibit the ERK1/2 pathway. The resulting changes in the proliferative activity of MG63 cells and the osteogenesis-related markers were analyzed.Results: The SVNs synthesized in the present study had a mean diameter of 27 nm. The encapsulation and drug-loading efficiencies were 52.03% ± 4.05% and 9.42% ± 0.66%, respectively. SVNs and SV exhibited optimum osteogenesis-promoting effects when the drugs were administered at a concentration of 0.25 µmol/L. The drug-induced activation of the ERK1/2 pathway reached a peak at 15 minutes after administration and then declined rapidly. From 24 hours to 7 days, SVNs and SV exerted an inhibitory effect on the ERK1/2 pathway rather than an activating effect. Throughout the whole experimental process, the regulatory effect of SVNs on the ERK1/2 pathway was significantly greater than that of SV. Inhibition of the ERK1/2 pathway by PD98059 markedly reduced the proliferative activity of the cells in all experimental groups. In addition, the ALP activity and the expression levels of the osterix (OSX) and osteocalcin (OC) proteins were drastically increased.Conclusion: SVNs significantly increased the effect of SV-induced osteogenic differentiation by strongly inhibiting the ERK1/2 pathway.Keywords: simvastatin-loaded nanomicelles, ERK1/2 pathway, dental implant restoration, osteogenic effectNiu MFeng XZhou LDove Medical PressarticleSimvastatin-loaded nanomicellesERK1/2 pathwayOsteogenic effectDental implant restorationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8165-8178 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Simvastatin-loaded nanomicelles ERK1/2 pathway Osteogenic effect Dental implant restoration Medicine (General) R5-920
spellingShingle	Simvastatin-loaded nanomicelles ERK1/2 pathway Osteogenic effect Dental implant restoration Medicine (General) R5-920 Niu M Feng X Zhou L The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells
description	Mao Niu,1,* Xianling Feng,2,* Lei Zhou3 1Department of Stomatology, School of Medical Technology and Nursing, Shenzhen Polytechnic, Shenzhen, 518055, China; 2Department of Pathology, School of Medical, Shenzhen University, Shenzhen, 518060, China; 3Center of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, 510280, China *These authors contributed equally to this work and should be considered as co-first authors Objectives: The present study aimed to clarify the role of the ERK1/2 pathway in simvastatin (SV)-loaded nanomicelles (SVNs)- and SV-mediated promotion of cell osteogenic differentiation and explore the molecular mechanisms by which SVNs exhibited a greater efficacy in promoting osteogenic differentiation than SV.Materials and methods: SVNs were synthesized using a dialysis method. MG63 cells were treated with 2.5, 0.25, and 0.025 µmol/L of the drug. The optimal drug dosage was determined by examining the proliferative activity and ALP activity of the MG63 cells. Subsequently, Western blot analysis was performed to analyze the levels of the phosphorylated ERK1/2 proteins in each experimental group at various time points. Finally, the inhibitor PD98059 was used to effectively inhibit the ERK1/2 pathway. The resulting changes in the proliferative activity of MG63 cells and the osteogenesis-related markers were analyzed.Results: The SVNs synthesized in the present study had a mean diameter of 27 nm. The encapsulation and drug-loading efficiencies were 52.03% ± 4.05% and 9.42% ± 0.66%, respectively. SVNs and SV exhibited optimum osteogenesis-promoting effects when the drugs were administered at a concentration of 0.25 µmol/L. The drug-induced activation of the ERK1/2 pathway reached a peak at 15 minutes after administration and then declined rapidly. From 24 hours to 7 days, SVNs and SV exerted an inhibitory effect on the ERK1/2 pathway rather than an activating effect. Throughout the whole experimental process, the regulatory effect of SVNs on the ERK1/2 pathway was significantly greater than that of SV. Inhibition of the ERK1/2 pathway by PD98059 markedly reduced the proliferative activity of the cells in all experimental groups. In addition, the ALP activity and the expression levels of the osterix (OSX) and osteocalcin (OC) proteins were drastically increased.Conclusion: SVNs significantly increased the effect of SV-induced osteogenic differentiation by strongly inhibiting the ERK1/2 pathway.Keywords: simvastatin-loaded nanomicelles, ERK1/2 pathway, dental implant restoration, osteogenic effect
format	article
author	Niu M Feng X Zhou L
author_facet	Niu M Feng X Zhou L
author_sort	Niu M
title	The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells
title_short	The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells
title_full	The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells
title_fullStr	The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells
title_full_unstemmed	The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells
title_sort	role of the erk1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in mg63 cells
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/e9aa2de7b3824ad8b37789a916fd36c8
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The role of the ERK1/2 pathway in simvastatin-loaded nanomicelles and simvastatin in regulating the osteogenic effect in MG63 cells

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