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Cited by 63Bone Tissue Engineering MaterialsMagnesium Alloys: Properties and ApplicationsBone Metabolism and Diseases

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Effect of magnesium ions/Type I collagen promote the biological behavior of osteoblasts and its mechanism

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Nie, Xiaojing, Sun, Xirao, Wang, Chengyue, Yang, Jingxin·2019·Regenerative Biomaterials
DOI 10.1093/rb/rbz033PMC PMC7233620
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Abstract

Type I collagen (Col I) is a main component of extracellular matrix (ECM). Its safety, biocompatibility, hydrophilicity and pyrogen immunogenicity make it suitable for tissues engineering applications. Mg2+ also control a myriad of cellular processes, including the bone development by enhancing the attachment and differentiation of osteoblasts and accelerating mineralization to enhance bone healing. In our studies, Mg2+ bind collagen to promote the proliferation and differentiation of osteoblasts through the expression of integrins and downstream signaling pathways. In order to clarify the biological behavior effect of 10 mM Mg2+/Col I coating, we performed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP), 4′6-diamidino-2-phenylindole (DAPI), Alizarin red staining and Rhodamine B-isothiocyanate (RITC)-labeled phalloidin experiments and found that 10 mM Mg2+ group, Col I-coating group, 10 mM Mg2+/Col I-coating group, respectively, promoted the proliferation and differentiation of osteoblasts, especially 10 mM Mg2+/Col I-coating group. We detected the mRNA expression of osteogenic-related genes (Runx2, ALP and OCN, OPN and BMP-2) and the protein expression of signaling pathway (integrin α2, integrin β1, FAK and ERK1/2), these results indicated that 10 mM Mg2+/Col I coating play an critical role in up-regulating the MC3T3-E1 cells activity. The potential mechanisms of this specific performance may be through activating via integrin α2β1-FAK-ERK1/2 protein-coupled receptor pathway.

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Figure 1 The process of Col I coating: Col I dissolved with glacial acetic acid-filtered coating plates for several hours at 37°C
Figure 1 The process of Col I coating: Col I dissolved with glacial acetic acid-filtered coating plates for several hours at 37°CCC BY · PubMed Central
Figure 2 OD values of NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group), Mg+COL (10 mM Mg2+/Col I-coating group) after incubation of MC3T3-E1 cells for 1, 3 and 5 days. One-way ANOVA (n = 5 per treatment group). *P < 0.05 versus control group
Figure 2 OD values of NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group), Mg+COL (10 mM Mg2+/Col I-coating group) after incubation of MC3T3-E1 cells for 1, 3 and 5 days. One-way ANOVA (n = 5 per treatment group). *P < 0.05 versus control groupCC BY · PubMed Central
Figure 3 The DAPI staining results for the NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group) and Mg+COL(10 mM Mg2+/Col I-coating group)
Figure 3 The DAPI staining results for the NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group) and Mg+COL(10 mM Mg2+/Col I-coating group)CC BY · PubMed Central
Figure 4 The cytoskeleton of osteoblasts were stained in NC (control group), Mg (10 mMMg2+ group), COL (Col I-coating group) and Mg+COL (10 mM Mg2+/Col I-coating group) (scale bar: 100 μm). Actin filaments were shown red and the nucleus were shown blue. One-way ANOVA (n = 3 per treatment group). *P < 0.05 versus control group
Figure 4 The cytoskeleton of osteoblasts were stained in NC (control group), Mg (10 mMMg2+ group), COL (Col I-coating group) and Mg+COL (10 mM Mg2+/Col I-coating group) (scale bar: 100 μm). Actin filaments were shown red and the nucleus were shown blue. One-way ANOVA (n = 3 per treatment group). *P < 0.05 versus control groupCC BY · PubMed Central
Figure 5 The ALP activity of NC (control group), Mg (10 mM Mg2+group), COL (Col I-coating group), Mg+COL (10 mM Mg2+/Col I-coating group) after incubation of MC3T3-E1 cells for 3, 5 and 7 days. One-way ANOVA (n = 5 per treatment group). *P < 0.05 versus control group
Figure 5 The ALP activity of NC (control group), Mg (10 mM Mg2+group), COL (Col I-coating group), Mg+COL (10 mM Mg2+/Col I-coating group) after incubation of MC3T3-E1 cells for 3, 5 and 7 days. One-way ANOVA (n = 5 per treatment group). *P < 0.05 versus control groupCC BY · PubMed Central
Figure 6 After incubation of 18 days, (a) the NC (control group), (b) Mg (10 mM Mg2+ group), (c) COL (Col I-coating group), (d) COL+Mg (10 mM Mg2+/Col I-coating group) of mineralization of ECM (scale bar: 50 μm)
Figure 6 After incubation of 18 days, (a) the NC (control group), (b) Mg (10 mM Mg2+ group), (c) COL (Col I-coating group), (d) COL+Mg (10 mM Mg2+/Col I-coating group) of mineralization of ECM (scale bar: 50 μm)CC BY · PubMed Central
Figure 7 After 7 days of incubation, the NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group), COL+Mg(10 mM Mg2+/Col I-coating group) that protein expression levels of FAK (a), integrin α2 (b), integrin β1 (c), ERK1/2 (d). One-way ANOVA (n = 3 per treatment group). *P < 0.05 versus control group
Figure 7 After 7 days of incubation, the NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group), COL+Mg(10 mM Mg2+/Col I-coating group) that protein expression levels of FAK (a), integrin α2 (b), integrin β1 (c), ERK1/2 (d). One-way ANOVA (n = 3 per treatment group). *P < 0.05 versus control groupCC BY · PubMed Central
Figure 8 The NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group), COL+Mg (10 mM Mg2+/Col I-coating group) that osteogenic-related genes expression levels of OPN (a), OCN (b), ALP (c), RUNX2 (d), BMP-2 (e) at 7 days were quantified by real-time PCR. One-way ANOVA (n = 3 per treatment group). *P < 0.05 versus control group
Figure 8 The NC (control group), Mg (10 mM Mg2+ group), COL (Col I-coating group), COL+Mg (10 mM Mg2+/Col I-coating group) that osteogenic-related genes expression levels of OPN (a), OCN (b), ALP (c), RUNX2 (d), BMP-2 (e) at 7 days were quantified by real-time PCR. One-way ANOVA (n = 3 per treatment group). *P < 0.05 versus control groupCC BY · PubMed Central
Figure 9 The potential mechanisms of integrinα2β1-FAK-ERK1/2 signaling in MC3T3-E1 cells
Figure 9 The potential mechanisms of integrinα2β1-FAK-ERK1/2 signaling in MC3T3-E1 cellsCC BY · PubMed Central

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Metadata

Authors
Nie, X., Sun, X., Wang, C., & Yang, J.
Affiliations
  • Jinzhou Medical University (CN)
  • Beijing Union University (CN)
Corresponding author
  • Wang, Chengyue
  • Yang, Jingxin
ORCID
Venue
Regenerative Biomaterials
Publisher
Oxford University Press (OUP)
Published
2019-10-30
Volume
7
Issue
1
Pages
53-61
ISSN
  • 2056-3418 (ISSN-L)
  • 2056-3426
DOI
10.1093/rb/rbz033
PMC
PMC7233620
OpenAlex
W2982515127
Cited by
63
References
0
Citations by year
2026: 7 · 2025: 14 · 2024: 15 · 2023: 12 · 2022: 6 · 2021: 8 · 2020: 1
FWCI
1.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Regenerative Biomaterials (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Science and Technology Fund of Liaoning Province (20180530071, 2019-MS-141)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Physical Sciences › Materials Science › Biomaterials › Magnesium Alloys: Properties and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
magnesium ions, type I collagen, osteoblast proliferation, osteogenic differentiation, alpha2beta1 integrin, focal adhesion kinase, ERK signaling, Runx2, alkaline phosphatase, MC3T3-E1 cells, bone tissue engineering, collagen coating

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