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. 2020 Nov;53(11):e12906.
doi: 10.1111/cpr.12906. Epub 2020 Oct 11.

Bioglass could increase cell membrane fluidity with ion products to develop its bioactivity

Longxin Yan  1 , Haiyan Li  1 , Weiliang Xia  1
Affiliations

Bioglass could increase cell membrane fluidity with ion products to develop its bioactivity

Longxin Yan et al. Cell Prolif. 2020 Nov.

Abstract

Objectives: Silicate bioactive glass (BG) has been widely demonstrated to stimulate both of the hard and soft tissue regeneration, in which ion products released from BG play important roles. However, the mechanism by which ion products act on cells on cells is unclear.

Materials and methods: Human umbilical vein endothelial cells and human bone marrow stromal cells were used in this study. Fluorescence recovery after photobleaching and generalized polarization was used to characterize changes in cell membrane fluidity. Migration, differentiation and apoptosis experiments were carried out. RNA and protein chip were detected. The signal cascade is simulated to evaluate the effect of increased cell membrane fluidity on signal transduction.

Results: We have demonstrated that ion products released from BG could effectively enhance cell membrane fluidity in a direct and physical way, and Si ions may play a major role. Bioactivities of BG ion products on cells, such as migration and differentiation, were regulated by membrane fluidity. Furthermore, we have proved that BG ion products could promote apoptosis of injured cells based on our conclusion that BG ion products increased membrane fluidity.

Conclusions: This study proved that BG ion products could develop its bioactivity on cells by directly enhancing cell membrane fluidity and subsequently affected cell behaviours, which may provide an explanation for the general bioactivities of silicate material.

Keywords: Bioglass; cell activity; membrane fluidity; silicon.

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Conflict of interest statement

The authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
Si of bioactive glass ions extracts could increase cell membrane fluidity. Fluorescence recovery after photobleaching (FRAP) experiment and generalized polarization (GP) value of cell membrane were used to evaluate membrane fluidity. A, Images of HBMSCs in FRAP experiment, which were treated with control medium or Si 1/128 medium. Images were shown at 0, 20, 40, 60, 80 s of whole FRAP experiment. B,C, Normalized fluorescence recovery curve of HUVECs and HBMSCs cultured with different media (n = 9). Fluorescence recovery on membrane was increased with the addition of Si. D, Laurdan fluorescence merged images, polarization value pseudo colour map and polarization value density histogram of HBMSCs cultured with control medium or 40ºC treatment in control medium or Si 1/128 medium. E,F, HUVEC and HBMSCs were treated with different media (n = 12). GP value of membrane was reduced with the addition of Si in the culture medium, which showed the increased membrane fluidity by Si. HBMSC, human bone marrow mesenchyme stem cell; HUVEC, human umbilical vein endothelial cell; NC, negative control
FIGURE 2
FIGURE 2
Si interacted with cell membrane to enhance cell membrane fluidity in a direct and physical way. A,B, GP values of cell membranes in HUVECs and HBMSCs were fast and reversibly changed with adding or removing Si (n = 9). C,D, FRAP results indicated that Si had rapid and reversible effects on cell membrane (n = 9). For each pair of graphs, the left side is the fluorescence image of the cells at 0 (bleaching time), and the right side is the fluorescence image of the cells at 50 s. E, The Laurdan fluorescence intensity was increased with time when the cells were cultured with Si 1/128, while the fluorescence spectrum did not change, indicating that the Si did not damage the cell membranes (n = 3). FRAP, fluorescence recovery after photobleaching; GP, generalized polarization; HBMSC, human bone marrow mesenchyme stem cell; HUVEC, human umbilical vein endothelial cell; NC, negative control
FIGURE 3
FIGURE 3
Hsp70 gene expression in HUVECs and HBMSCs after stimulated by Si ion containing BG ion extract (n = 3). *P < .05, and **P < .01 with two‐way analysis of variance. HBMSC, human bone marrow mesenchyme stem cell; HUVEC, human umbilical vein endothelial cell; NC, negative control
FIGURE 4
FIGURE 4
Biological effects of Si on cells were closely related to cell membrane fluidity. A, GP value of HUVECs cultured with Si, CHS and Si + CHS (n = 9). B, Images of wound healing and Transwell assay of HUVECs treated with Si, CHS and Si + CHS (n = 3). C, Quantification of HUVECs migration ability based on wound healing experiments. Si treatment increased HUVEC migration, while CHS treatment inhibited HUVEC migration. Co‐treatment of Si and CHS inhibited HUVEC migration to the same level as CHS treatment. D, GP value of HBMSCs cultured with Si, CHS and Si + CHS (n = 9). E, ALP staining of HBMSCs treated with Si, CHS and Si + CHS (n = 3). F, Gene expressions of ALP and COLI in HBMSCs treated with Si, CHS and Si + CHS (n = 3). Si treatment increased HBMSC osteogenic differentiation while CHS treatment inhibited HBMSC osteogenic differentiation. Co‐treatment of Si and CHS inhibited HBMSC osteogenic differentiation to the same level as CHS treatment. ALP, alkaline phosphatase; CHS, Cholest‐5‐en‐3‐ol (3β)‐, 3‐(hydrogen butanedioate); COLI, collagen type I; GP, generalized polarization; HBMSC, human bone marrow mesenchyme stem cell; HUVEC, human umbilical vein endothelial cell; NC, negative control
FIGURE 5
FIGURE 5
Si could promote apoptosis, especially early apoptosis, of injured HUVECs. A,B, The apoptosis ratio of healthy HUVECs treated with Si 1/64, Si 1/128 or Si 1/256 (n = 3). Si had no significantly affects on healthy HUVECs apoptosis. C,D, The effects of Si on apoptosis ratio of HUVECs in different cell injury models (n = 3). Si significantly increased apoptosis of HUVECs in all apoptotic models. Si significantly increased early apoptosis (marked by phosphatidylserine eversion) of HUVECs. HUVEC, human umbilical vein endothelial cell; NC, negative control
FIGURE 6
FIGURE 6
Results obtained from Affymetrix gene expression chip and PEX100 protein activation chip analysis on the HBMSCs cultured with or without Si. A, The scatter plot of gene expression (X axis for Si 1/128 treatment, Y axis for NC). Differentially expressed genes were shown as class‐3. B, Cellular component distributions of differentially expressed genes according to Gene Ontology. 45.8% of these genes were membrane localized and 33.4% were nucleus localized. Other component were 20.8% only. C, KEGG cluster analysis according to gene expression data. D, KEGG cluster analysis according to protein activations chip. These cluster data showed that numerous base signal pathways were activated, including G protein signal pathways, cytokine pathways, ion channels, PI3K‐IP3 pathways. HBMSC, human bone marrow mesenchyme stem cell; NC, negative control
FIGURE 7
FIGURE 7
Simulations of the relationship between membrane fluidity and signal transductions. A,B, Effects of membrane fluidity on signal system with resting‐state signal, representing the effects of Si on cells for a long term. For cascade system structures, as T1, T2, T3, increased membrane fluidity had no significant influence on protein activation ratio, which were waved around. However, increased membrane fluidity significantly increased signal output strength, which indicated the long‐term benefit of enhanced membrane fluidity on the signal system. C,D, System responded with step signal. Reactions of signal activations and recovery were more quickly in superfluid group than the normal group. In addition, the secondary response of superfluid group was better than that of the normal group
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