*3.1.10 Other markers of periodontal disease*

Other biomarkers have been analyzed to determine periodontitis. One of these is chondroitin sulfate, which is a natural glycosaminoglycan (GAG) present in the extracellular matrix [31]; chondroitin sulfate is recognized for its immunomodulatory effects, such as the reduction of nuclear translocation NF-κB, the decrease in the production of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α), and the decrease in expression and activity of nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) [32]. Another molecule that has been proposed as a possible biomarker is MUC-4. Mucins are high-molecular-weight glycoproteins, are involved in diverse biological functions, are members of transmembrane mucin family, and are expressed in airway epithelial cells and body fluids like saliva, tear film, ear fluid, and breast milk [33]. It has been reported that the production of MUC-4 could be regulated by inflammatory cytokines [34].

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*Use of Biomarkers for the Diagnosis of Periodontitis DOI: http://dx.doi.org/10.5772/intechopen.85394*

Saliva is a seromucous secretion, consisting of 99% water; however, saliva is also composed of glycoproteins, phosphate ions, bicarbonate, sodium, chlorine, fluorine, calcium, and potassium and has a neutral pH [35], which forms a film of liquid consistency that covers the surface of the oral mucosa, with the purpose of lubricating it and keeping it moist among many other characteristics for the maintenance of oral health [36]. The composition of saliva varies from one place to another in the oral cavity of each individual [35]. If there are changes in its composition, there may

be significant alterations in deterioration of the health of the host [37].

cardiovascular diseases, diabetes, HIV, oral cancer, and oral diseases [40].

*3.2.1 Proteins (cytokines) determined in saliva that could be used as biomarkers*

In our review we observed that there are about 15 works that were dedicated to investigate the possible use of these proteins determined in saliva as biomarkers to determine periodontitis. We can say that of all the works, the majority focuses on comparing healthy groups with periodontitis; only three researches include the group of gingivitis, which indicates that this group should be used more for this type of studies. We need to remember that gingivitis is considered an intermediate stage that may or may not lead to periodontitis [41], and if the patient performs good dental hygiene in combination with the treatment, in general, progression to

On the other hand, the cytokine that has been most explored and that better results have given as biomarkers to detect in saliva is the cytokine IL-1β [43–48]; this must be due to the recognized importance of interleukin-1β, as an important

However, other cytokines such as IL-6 and IL-2 have also been explored [43, 44, 48, 50]; IL-6 is recognized for playing a role as a pro-inflammatory cytokine acting on bone resorption in the presence of infections [51]. Regarding IL-2, a study that investigated cytokine profiles at different stages of the development of periodontitis found that levels of mRNA for IL-2 were significantly associated with the phase of resolution of the disease [52]. This agrees with reports that IL-2 has been implicated

Regarding MCP-1, Gupta et al. [54] conducted a study in 45 patients with an average age of 43 years for healthy patients and 41 for patients with periodontitis, with results similar to Nisha et al. [55]. In both studies it was found that the levels of MCP-1 in saliva can be a good biomarker for the development of periodontal disease. One difference between the studies is that Nisha's work included a group of

Regarding the possibility of using prostaglandin E2 (PGE2) as biomarkers in saliva to diagnose gingivitis, Syndergaard et al. [56] conducted a study with 80 participants, 40 without gingivitis and 40 with gingivitis, and found that the levels of PGE2 in the group with gingivitis were significantly higher compared with the

Due to the described characteristics of saliva, several authors have claimed that these salivary constituents may actually be useful indicators of both local and systemic disorders. These revelations have formed the basis of the field of saliva diagnosis and, therefore, have triggered research that culminated in the identification of saliva-based biomarkers for disorders ranging from cancer to infectious diseases [38]. In addition to the above, saliva has several advantages when compared to other sources for diagnosing diseases since saliva is easily collected and stored and ideal for early detection of disease as it contains specific soluble biological markers [39]. Saliva has been used to diagnose diseases as diverse as autoimmune disorders,

**3.2 Biomarkers determined in saliva**

periodontitis can also be stopped [42].

in the stimulation of osteoclasts [53].

mediator in the pathophysiology of periodontitis [49].

patients with gingivitis, while Gupta's study does not include it.
