The objective of the research was to analyze and compare the PLGF in the saliva of healthy individuals and periodontitis patients, in general, and investigating the role of PLGF in the pathogenesis of periodontitis and correlating PLGF’s levels with the severity of periodontitis, in specific. PLGF in saliva was detected and quantified in all the samples that were subjected to analysis, and there was a quantifiable difference between health and periodontitis.

Several biomarkers and their biological actions in periodontal pathology have been extensively discussed in the literature. However, the interconnections among these significant biological molecules, signaling pathways, and reciprocations are not entirely comprehensible yet. This has led to assessing the role of these markers of inflammation in the periodontal tissues, GCF, saliva and serum. Various biomarkers have been extensively analyzed in health and disease and a quantifiable difference in most of the evaluated biological molecules has been reported [19,20,21].

An Italian scientist Dr. Maria Graziella Persico in 1991, first reported PLGF after its discovery. It was recognized when analyzing the angiogenic capacity of the human placenta, hence this biological molecule was named “the placental growth factor” [7]. As described earlier, PLGF is representative of the VEGF family that also includes the structurally and functionally connected angiogenic factors VEGF-A to VEGF-E. Although identified first in the placenta, PLGF is more than a specific maternal biomarker. PLGF expression is high during the development of the fetus in the placenta, heart, lung, thyroid, brain, skeleton muscle, and gingival epithelium but lowers in adulthood. PLGF is also expressed in the heart, lung, thyroid, adipose tissue, and skeletal muscle of adults [10]. Whether PLGF is a potential biomarker of disease or has a role in targeted vascular disease therapies remains the focus of continuing research. It has been reported that PLGF is present in human oral fluids and is a biomarker for preeclampsia and gestational diabetes mellitus [22]. Although PLGF is discussed in relation to several inflammatory conditions as atherosclerosis and rheumatoid arthritis, to the best of our knowledge the present study may be the first that is examining salivary PLGF levels and periodontitis.

In this study, salivary PLGF levels were compared in periodontal health and in cases of moderate or severe periodontitis with the consideration that concentrations of unstimulated saliva analytes are not affected by diurnal salivary flow rate as per Carpenter [23]. The results were not statistically significant with regard to PLGF levels in health and periodontitis. Also, no significant correlation between the severity of the periodontitis and the levels of PLGF were noted, except for a statistically significant negative correlation of PLGF levels with PPD and BOP, that has not been reported earlier, leading to the possibility of PLGF to be quantitatively lower in a local inflammatory condition such as periodontitis. It could offer the explanation that PLGF may be protective instead of pro-inflammatory as reported in maternal conditions. In another study [24], it was found that reduced PLGF activity is involved in anti-inflammatory effects.

Sert et al. [5], evaluated the levels of serum IL-1β, IL-6, TNF-α, IL-10, VEGF, PLGF, and sVEGFR-1, and − 2 in the association between periodontal disease and adverse pregnancy outcomes; according to their results, there were no significant differences in the serum PLGF level between health, gingivitis, and periodontitis, which is also pointing at the inconsistencies of the role of PLGF for a definitive conclusion. Conversely, Chaparro et al. [18]. , in a study on maternal oral fluids (i.e. saliva and GCF) concentrations of PLGF and sFlt-1 in conjunction with periodontal inflammatory status early in pregnancy (11 to 14 gestation weeks) found that maternal PLGF concentrations in GCF were significantly increased in pregnant women with periodontitis who later develop GDM, while PLGF concentrations in saliva did not show statistically significant differences which is similar to our results, and they emphasized on clarification of the role of placental mediators in periodontal tissues. Tseng et al. [25] have reported an upregulation of PLGF and Leblebicioglu et al. [26]. , , observed that PLGF levels of GCF increase in wounding and inflammation. Our results indicate salivary PLGF to be lower in periodontitis as compared with health. In the context of our study all these reports about pregnant women open up further challenges to interpret our observations of PLGF levels in saliva independent of pregnancy, as to whether to attribute a pro-, or anti-inflammatory behavior with regard to periodontitis.

We also assessed the PLGF level in relation to gender (the presence of PLGF in saliva was confirmed in both males and females); females had a higher mean value yet the difference between both genders was not statistically significant (p > 0.05). Additionally, there was no significant difference between groups 1 and 2 (p > 0.05) in terms of a specific gender. Although none of the previous studies in the literature have mentioned this association, it can be implied that PLGF can be detected in both genders (not necessarily only in females during pregnancy).

The current investigation has accomplished the general objective of analyzing and comparing PLGF in the saliva of health and periodontitis and a quantifiable difference between these two groups was noted, though not statistically significant. Specifically, the role of PLGF in the pathogenesis of periodontitis is not conclusive. Regarding the correlation of PLGF levels with periodontitis, it was observed that PLGF might be potentially anti-inflammatory in action, viewing its relationship with two significant variables, i.e., BOP and PPD. If the biologic behavior of PLGF is comparable to VEGF, then it is plausible that in periodontitis, PLGF may not be released as it may be bound to tissue. Clarification of PLGF activity with respect to periodontitis needs more research.