## 4 Discussion
This could be due to the galvanic situation present in the IAC, which could have enhanced the metal ion release from the couplings and therefore enhanced the adverse reactions. Another reason for this could be the composition of the IAC vs. UI. The soluble Co and V released from Co- and Ti-based abutment alloys, respectively, are among the most toxic metals, and have been shown to reduce the proliferation and viability of osteoblasts and other periprosthetic cells [32]. Although the influence of the implant-abutment mismatch on cell viability was only statistically significant at some time points, there was an obvious general trend showing that the larger the mismatch, the more favorable the cell viability. In other words, osteoblastic cell viability was inversely related to the abutment size, which means that the groups corresponding to the platform-matched couplings had less viability than the platform-switched groups within the same abutment material. The most logical explanation to this particular cell response could be that less ion is released from platform-switched groups, as was confirmed in earlier publications [8; 9]. This could correlate to previously reported findings that the viability of osteoblasts was inversely proportional to the particle and ion concentration [33; 34]. Although apoptosis is a normal fate for the majority of osteoblasts [35], the stimulation of osteoblast apoptosis reduces bone formation in the periprosthetic region, which could contribute to the total loss of bone volume around dental implants. It was evident in the present study that stimulated osteoblasts undergo higher rates of apoptosis. This finding was also supported by the upregulation of CASPASE-8 production after 1 day of exposure in most test groups. Similarly, [PERSON] et al. found that Ti induced a caspase-dependent apoptosis of osteoblasts [36]. Although the authors used Ti particles rather than actual implants, as in the present study, it is important to bear in mind that metal ions are also released from the particles themselves, as well as directly from implant surfaces [11]. Therefore, it is difficult to anticipate whether the cellular reactions in response to particle stimulation in earlier studies were related to the particles per se, or to the ions released from such particles, as each form acts biologically through different metabolic pathways [10]. Interestingly, the platform-matched groups demonstrated higher levels of apoptosis compared to the platform-switched groups within the same material, and this again could be due to the higher amounts of metal ions released from the platform-matched groups [8]. The results of the present study show that the IAC, mostly the platform-matched groups, have a profound impact on genes that code for inflammatory cytokines and genes involved in bone homeostasis. Although the upregulation of IL-6 was not remarkable in all test groups, it was noticeable in the platform-matched groups after 24 hrs of exposure, which could be due to the higher ion release, as explained earlier. It has been demonstrated by several investigators [11; 27; 28; 29; 37; 38] that titanium ions and particles, as well as CoCr, increased the signal levels of IL-6 in a dose-dependent manner. On the other hand, [PERSON] et al. showed that the release of IL-6 from Ti-stimulated osteoblast-like cells occurred in a time-dependent manner, which disagrees with the findings of the present experiment [37]. This apparent contrast could be attributed to the lower cell number caused by higher apoptotic rates and compromised viability after longer exposure periods [33], based on the assumption that only viable cells are capable of releasing IL-6 [32], which could also explain the downregulation observed in some genes after longer incubation periods. However, a statistical regression analysis to correlate cell vitality results with gene expression was not performed in the current study, limiting further anticipation of the data.