الفهرس 
Introduction .Only 14 pages are availabe for public view
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Abstract
Periodontal disease is multifactorial infection induced by a complex of bacterial species that interact with host tissues and cause destruction of the periodontal structures, including the supporting tissues of the teeth, alveolar bone and periodontal ligament (Könönen et al., 2019).
The bacterial biofilm formation initiates gingival inflammation; however, periodontitis initiation and progression depend on dysbiotic ecological changes in the microbiome in response to nutrients from gingival inflammatory exudates and tissue breakdown products that enrich some species and anti-bacterial mechanisms that attempt to contain the microbial challenge within the gingival sulcus area once inflammation has initiated (Tonetti et al., 2018).
Current evidence supports multifactorial disease influences, such as smoking, diabetes mellitus, obesity, metabolic syndrome, osteoporosis, and low dietary calcium and vitamin D and other immunoinflammatory responses that make the dysbiotic microbiome changes more likely for some patients than others and likely influence severity of disease for such individuals (Tonetti et al., 2018).
During periodontitis, the pathogen triggers the white blood cells of the innate immune system to release proinflammatory mediators such as cytokines that play a vital role in the progression of the inflammation process of periodontitis. In addition, these pathogens can activate the acquired immune system that contributes to the release of more cytokines and chemokines that cause permanent bone damage and irreversible periodontal attachment loss (Andrukhov et al., 2011).
Cytokines are defined as soluble small proteins (” " ~ " ”5–20 kDa) which bind to specific receptors on certain cells, stimulate some internal cellular changes, and cause multiple genetic and chemical regulations (Papapanou et al., 2018).
There are two different types of inflammatory cytokines: proinflammatory cytokines that are involved in inflammatory reactions including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-α), and anti-inflammatory cytokines that regulate or control the pro-inflammatory cytokine response including interleukin-4 (IL-4), interleukin-1 receptor antagonist (IL-1RA) and interleukin-10 (IL-10) (Zhang and An, 2007).
Nonsurgical periodontal therapy (NSPT) aims at mechanical removal of bacterial plaque from the tooth surface and it is considered the ”gold standard” of periodontal therapy. This procedure decreases the number of Gram-negative bacteria in favor of Gram-positive bacteria as well as reduces the overall number of microorganisms in periodontal pockets and decreases amount of proinflammatory cytokines (Stańdo and Lewkowicz, 2019).
Traditional clinical periodontal diagnostic parameters used include probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), plaque index (PI), and radiographs assessing alveolar bone level. They are limited, in that only disease history, not current disease status, can be assessed (Armitage, 2004).
Recent methods in oral and periodontal disease diagnostic research are identifying periodontal risk which is quantified by objective measures like biomarkers which are diagnostic tools to measure periodontal disease at the molecular, cellular, tissue, and clinical levels. The biological media for detecting periodontal disease biomarkers include gingival crevicular fluid (GCF), saliva, serum, subgingival plaque and tissue biopsies (Ghallab, 2018).
The major attraction of GCF as a diagnostic marker is the site-specific nature of the sample which may offer the basis for patient-specific diagnostic tests for periodontal disease. Moreover, simplicity of its use along with a level of reliability and low cost favors its use over other modalities (Bibi et al., 2021).
The discovery of new biomarkers will aid in the development of new therapeutic approaches via host modulatory drugs for periodontal disease treatment leading to more individualized, targeted treatments for oral health (Bibi et al., 2021).
In 2008, Lin et al. identified a secreted protein known as interleukin 34 (IL-34) with a high functional selectivity represented by stimulating monocytes survival in a colony-stimulating factor receptor (CSF-1R) dependent manner. IL-34 mRNA is expressed in several tissues, including the heart, brain, lungs, liver, kidneys, spleen, thymus, testes, ovary, small intestine, prostate, and colon, as well as -spleen.
Many studies such as (Wei et al., 2010), (Wang et al., 2012), (Ma et al., 2012), (Greter et al., 2012) provided insight into IL-34 biology, but many questions remain unanswered, specifically in terms of its function. High expression of IL-34 correlates with disease severity in autoimmune diseases (Sjögren’s syndrome, Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA), inflammatory diseases (liver fibrosis, kidney disease and inflammatory bowel disease. In contrast, IL-34 plays a protective role in some diseases, such as atopic dermatitis, Alzheimer’s disease, breast cancer and head and neck cancer (Lelios et al., 2020).
In periodontal disease, IL-34 can be considered a potential proinflammatory biomarker since, as shown in Bozkurt Doğan et al. (2021) GCF IL-34 levels were higher in patients with periodontitis but decreased after NSPT. On the contrary, Lira-Junior et al. (2021) found that salivary levels of IL-34 were significantly lower in the periodontitis group compared to both healthy groups and gingivitis. After receiving NSPT at 3- and 6-months post-treatment, IL-34 significantly increased 3 months later compared to baseline.
Therefore, further studies must be carried out to better understand the possible role of IL-34 whether it is a proinflammatory or anti-inflammatory cytokine in the pathogenesis of periodontal diseases and to evaluate the change of its levels in GCF in patients with periodontal disease after NSPT.