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Söhling, et al.
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           Figure 7. MSCs immune response to PLA/BG composites. Gene expression of inflammatory markers MAPK-8, MAPK-14, and IL-6 as well
           as protein expression of IL-6 were measured in the cells/supernatant cultured in the presence of different BG concentrations (n=5). (A) With
           increasing BG content, there is a decrease in IL-6 gene expression. For PLA/BG 10%, IL-6 gene expression after 24 h significantly decreases
           compared to PLA/BG10% after 72 h and 168 h. (B) No inhibition of IL-6 release by BG was observed. IL-6 levels remain relatively constant
           regardless of BG content and time period. (C) A significant decrease in MAPK-8 gene expression is also evident for cells cultured in contact
           with PLA/BG 10% and PLA/BG 20%. (D) For MAPK-14, an increase in expression can be detected at a BG content of 5% after 72 h and
           168 h.


                                                               The present study shows  the OD of MSC under the
                                                               influence of BG.
                                                                   The  MSC  gene  expression  profile  shows  a
                                                               characteristic course during the different phases of OD.
                                                               In this experiment, the focus was on the early phase of
                                                               OD up to day 7. For this phase, a significant increase in
                                                               the ALP gene expression was proven . This is in line
                                                                                               [46]
                                                               with our experimental outcomes. For MSCs cultured in
                                                               standard medium on BG20, a significant increase in ALP
                                                               gene expression was measured at day 7 compared to the
                                                               PLA control.
           Figure 8. Gene expression of IL-6 (A) in MSC cultivated 72 h in   As an essential transcription factor for OD, RUNX2
                                                                                                            [47]
           the presence of BG20 is dependent on calcium ions released by   is expressed in the early phase after induction of OD .
           the BG content. Calcium ions were chelated by presence of EGTA   Here, RUNX2 gene expression was increased when the
           modifying  relative  mRNA  expression  of  IL-6  in  MSC  cultured   cells were cultured on BG10 and BG20, albeit without
           with BG20 (n=3). *Shows P<0.05 versus indicated group. Results   statistical  significance  compared  to  PLA  control.
           are  mean  values  of the  three  measurements  and  their  standard   Significant decrease of RUNX2 gene expression in MSC
           deviation.
                                                               cultivated on BG20 has been shown after 72 h and 168 h.
                                                               The rapid decline of RUNX-2 expression as one initial step
           material  of  BG  (G5  glass)  and  PLA  enhanced  the   of OD in MSC is also congruent with previously reported
           differentiation  of  EPC  and  their  angiogenic  activity .   work on osteogenic MSC differentiation . Nevertheless,
                                                                                                [35]
                                                        [45]
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