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Biomarkers in periodontal disease

Pavan Kumar A

Periodontics, Kamineni Institute of dental sciences, India

E-mail : pavankumar2524@gmail.com

Jagdish Reddy G

Periodontics, Kamineni Institute of dental sciences, India

Raja Babu P

Periodontics, Kamineni Institute of dental sciences, India

DOI: 10.15761/DOCR.1000111

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Introduction

Periodontitis is a group of inflammatory diseases that affect the connective tissue attachment and supporting bone around the teeth whose initiation and progression depends on the presence of virulent microorganisms capable of causing disease [1]. Periodontitis is considered to be a multifactorial disease with no clear cut etiology, so its identification and early diagnosis becomes more difficult [2]. The current clinical diagnostic parameters were introduced more than 50 years ago. But all the methods provide disease severity rather than disease activity.

A biomarker is a substance used to indicate a biologic state and is an objective measure to evaluate the present and future disease activity. It is defined as – A substance that is measured objectively and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention [3]. Various biological media like saliva, serum and gingival crevicular fluid are used to determine biomarkers in periodontal health and disease. A single biomarker will not able to predict periodontal disease activity and severity. So combinations of biomarkers are used to predict the disease activity. [4].

Advantages of traditional diagnostic techniques

Easy to use, Cost effective, Non invasive, Measures disease severity [5].

Limitations of traditional periodontal diagnostic techniques

  • a) Clinical and radiological measurements of attachment loss are not precisely accurate
  • b) Full mouth recording is necessary because of the site specific nature of periodontal disease progression.
  • c) Individual susceptibility to periodontitis varies both genetically and over time
  • d) All clinical diagnostic techniques provide information about past disease activity and are unable to

Need for biomarker

Under diagnosis periodontal therapy leads to failure of periodontal treatment. For that researchers phrased biomarkers that indicated the presence or absence of periodontal disease [6]. The biological media of choice included saliva, serum and gingival crevicular fluid.

Proteomic biomarkers

The word "proteome" is a blend of "protein" and "genome", and was coined by Marc Wilkins. The proteome is the entire complement of proteins, including the modifications of a particular set of proteins. Proteomics offers a new approach to the understanding the changes occurring as oral micro-organisms adapt to environmental change within their habitats in the mouth [8].

Pyridinoline cross-linked carboxyterminaltelopeptide of type I collagen

Type I collagen is major collagen present in mineralized tissues. The degradation products of collagen act as markers for bone metabolism. The degradation products of collagen are pyridinoline, deoxypyridinoline, N-telopeptides and C-telopeptides. Increased levels of ICTP are associated with most of pathogens including T. forsythensis, P. gingivalis, P. intermedia, and T. denticola [9]. Non-surgical mechanical therapy doesn't not significantly reduce ICTP and IL-1 levels [10]. Contrary to this, SRP and local drug delivery lead to rapid reductions in GCF ICTP levels [11].

Osteocalcin

Osteocalcin is non collagenous protein. It is predominately present in mineralized tissues. It is produced by osteoblasts, help in bone remodeling. Increased levels of osteocalcin are associated with rapid bone remodeling. The levels of osteocalcin are remain unchanged in patients with gingivitis [12]. Osteocalcin levels are increased in periodontitis [13].

Alkaline phosphatase (ALP)

ALP is a catalyzing enzyme that accelerates the removal of phosphate groups in the 5 and 3 positions from a variety of molecules, including nucleotides, proteins, and alkaloids. Although it is present in all tissues, ALP is particularly concentrated in the bone, liver, bile duct, kidney and placenta. The enzyme is likely to be largely derived from the periodontal tissues [14]. The major source of ALP in early inflammation is polymorphonuclear leukocyte [15]. There is a significant correlation of ALP with pocket depth and inflammation. There is a relationship between attachment loss in the periodontitis group to a drop in ALP activity in serum [16]. Contrary to these results,the measurements of periodontal destruction (probing depth, gingival bleeding, and suppuration) are related to higher levels of ALP in saliva [17]. As a predictive indicator for the future periodontal breakdown, ALP may serve as a marker in periodontal treatment planning and monitoring.

Cathepsin B

Cathepsin B is responsible for proteolysis. Macrophages produce Cathepsin B in GCF. Cathepsin B levels are increased in periodontitis. It levels are increased while progression of the periodontal disease. The levels of Cathepsin B are useful for differeniatiting periodontitis from gingivitis [16] and also helpful for proper treatment plan [17].

Matrix metalloproteinases

Matrix metalloproteinases (MMPs) are genetically distinct but structurally related zinc dependent metalloendopeptidases. MMPs are host proteinases responsible for both tissue degradation and remodeling. MMPs degrade extracellular matrix and further potentiate proteolysis and inflammation by processing of bioactive non-matrix substrates, such as cytokines, chemokines and growth factors, and also by activating other MMPs.

The 23 MMPs expressed in humans can be classified into different subgroups based on their primary structures and substrate specificities: Collagenases (MMP-1, -8 and -13), Gelatinases (MMP-2 and -9), Membrane type MMPs (MT-MMPs, MMP-14, -15, -16, -17, -24 and -25) and other MMPs. In the healthy condition, the periodontal ligament apparatus is protected from matrix metalloproteinases mediated proteolytic attack by tissue inhibitors of metalloproteinases (TIMP) [18].

Collagenase-2 (MMP-8)

MMP-8 is also called collagenase-2.It is predominant collagen in GCF. Increased levels of MMP-8 in GCF is associated with severity of periodontitis. It is released from PMNs during maturation. Increased levels of MMP-8 are signify conversion of gingivitis into periodontitis. No associations are found between MMP-8 levels and bone loss [18]. MMP-8 levels reflect soft tissue destruction and periodontal response to treatment. It is believed that MMP-8 may serve as a proinflammatory marker, but not as a discriminating marker for chronic periodontitis and gingivitis [19]. It is found that 18-fold increase of MMP-8 in patients experiencing active periodontal tissue breakdown as compared with patients under stable condition [19].

Gelatinase (MMP-9)

Gelatinase (MMP-9), another member of the collagenase family, is produced by neutrophils and degrades collagen extracellular ground substance. There is a twofold increase in mean MMP-9 levels is reported in patients with recurrent attachment loss. After giving one dose of systemic metranidazole, the levels of MMP-9 in mouth rinse samples from patients with initial elevated MMP-9 concentrations markedly decreased [20]. Given these results, future use of MMP-9 in oral diagnostics may best serve as a guide in periodontal treatment monitoring [21].

Collagenase-3 (MMP-13)

Collagenase-3, referred to as MMP-13, is another collagenolytic MMP with exceptionally wide substrate specificity. MMP-13 is expressed by sulcular epithelial cells, endothelial cells, macrophage-like cells, fibroblasts, plasma cells and osteoblasts. The expression of MMP-13 is specifically induced in undifferentiated epithelial cells during chronic inflammation due to exposure to cytokines and collagen [17].MMP-13 has also been implicated in peri-implantitis. Elevated levels of both MMP-13 and MMP-8 are correlate with irreversible peri-implant vertical bone loss around loosening dental implants [17]. In patients with untreated periodontal disease, collagenase present predominantly in the active form [21]. In the future, MMP-13 may be useful for diagnosing and monitoring the course of periodontal disease as well as tracking the efficacy of therapy.

Myeloperoxidase

Neutrophil-derived myeloperoxidase (MPO) is contained in primary (azurophilic) granules from neutrophils and catalyzes the formation of hypochlorous acid (HOCl), a powerful antibacterial agent, which reflects the strength of oxidative stress.MPO can inactivate pathogenic microbes by generating reactive oxygen species, oxidatively activate latent proMMP-8 and 9, as well as inactivate TIMPs. Thus, MPO can also oxidatively potentiate MMP-cascades in periodontal tissue destruction, becoming potentially deleterious. The increased MPO activity is attributed to increased infiltration and degranulation of PMNs. During therapy salivary peroxidase concentrations are declined below the control values [22].

Calprotectin

Calprotectin is released from neutrophils. It is a calcium and zinc binding protein, has both antimicrobial and antifungal activity and play a vital role in inflammation. It inhibits immunoglobulin production and act as a proinflammatory protein. Increased expression of calprotectin at the site of inflammation offer protection against bacterial invasion to epithelial cells especially P.gingivalis [23]. Calprotectin appears to improve resistance to P. gingivalis by boosting the barrier protection and innate immune functions of the gingival epithelium.

Osteonectin

It is a secreted protein .It is acidic in nature and contains cysteine; base membrane protein BM-40.It has strong avidity to hydroxyapatite and collagen. It plays a vital role in early phase of mineralization so it can act as a sensitive marker for detection of periodontitis. The sensitivity of this marker for diagnosing periodontal disease more when compare with N-propeptide of typeI collagen [17]

Osteopontin (OPN)

OPN is released by both osteoblasts and osteoclasts. The concentration of OPN is higher at the clear zone where osteoclasts are attached. It helps in bone remodeling. In periodontitis, OPN levels are increased. There is a positive correlation between increased levels of OPN to probing pocket depth [24,25]. When nonsurgical periodontal treatment is provided GCF OPN levels are significantly reduced [26].

Cystatins

Cystatins are act as biomarkers for periodontal disease diagnosis. Many isoforms of Cystatins are secreted into saliva and GCF in periodontitis. Cystatin C in saliva act as a biomarker for diagnosing periodontitis as it levels are increased in saliva in periodontitis. GCF Cystatins are poor biomarkers for periodontitis when compared with Cystatins in saliva [27].

Fibronectin

Fibronectin is a glycoprotein that promotes selective adhesion and colonization of certain bacterial species .it is involved in chemotaxis, migration, inflammation, wound healing and tissue repair. Changes in oral cleanliness may contribute to the rapid fluctuations in salivary proteases and epithelial cell fibronectin [28]. There are no statistically significant differences between pre- and post-treatment concentrations of fibronectin, whether expressed as micrograms fibronectin/micrograms protein or as micrograms fibronectin/ml saliva [29].

Lysozyme

Lysozyme is a proteolytic enzyme, mainly present salivary gland secretions. It damages bacterial cell wall. Patients with low lysozyme activity in saliva are more prone to periodontal disease. Levels of lysozyme is inversely proportional to plaque accumulation [30]. Many studies are shown that lysozyme concentrations are decreased in periodontitis [31].

Lactoferrin

Lactoferrin is mainly secreted from salivary glands. It is an antibacterial iron binding glycoprotein. Increased levels of lactoferrin in saliva are strongly associated with periodontitis [31].

Immunoglobulins

The predominant immunoglobulin in saliva is secretory IgA (sIgA) which is derived from plasma cells in the salivary glands. There are two subclasses of IgA – IgA1 and IgA2. IgA1 is predominates in serum while IgA2 is found in higher concentrations in external secretions [33]. Saliva from treated periodontitis patients has higher IgA and IgG levels than saliva from control subjects. These higher antibody levels are observed for periodontal pathogens (P. gingivalis and Treponemadenticola), but also for the normal inhabitant of the oral cavity Streptococussalivarius [34]. Significantly elevated levels of IgG antibody to A. actinomycetemcomitans are found [35]. High level of salivary IgA is directed against bacteria in dental plaque and may protect against the development of gingivitis [36].

Platelet activating factor

Platelet activating factor, also known as PAF, is a potent phospholipid activator and mediator of many leukocyte functions including platelet aggregation, degranulation, inflammation, and anaphylaxis. It is produced by platelets, endothelial cells, neutrophils, monocytes, and macrophages. A significant positive correlation is observed between the level of PAF in saliva and measures of periodontal inflammation [37]. Thus, initial periodontal therapy is reduced salivary PAF levels in concert with improvements in clinical estimates of marginal and sub marginal periodontal inflammation suggesting that PAF may participate in inflammatory events during periodontal tissue injury and disease [38].

Epidermal growth factor

Epidermal growth factor stimulates cell growth, proliferation and differentiation by binding to its receptor EGFR. The elevated rate of salivary EGF secretion in aggressive patients may be associated with the pathogenic mechanisms of aggressive periodontitis [39].

Platelet-derived growth factor: In vitro and in vivo studies suggest PDGF is the most thoroughly described growth factor associated with periodontal health. There are different isoforms of PDGF (PDGF-AA, -AB, -BB), and all have been shown to have a fibroblast proliferative activity [40]. PDGF is present in increased levels in the human inflamed gingiva and is mainly localized to the pocket epithelium. It is possible that expression of PDGF contributes to the inflammatory changes those occur during periodontal diseases. PDGF supports the healing. Since PDGF is chemo tactic for fibroblasts, it induces collagen synthesis, stimulates fibroblasts to synthesize the proteoglycans for extracellular matrix development [41]. Thus decrease in PDGF can be a useful marker for periodontal disease [42].

Vascular endothelial growth factor (VEGF): VEGF is a key regulator of physiological and pathological angiogenesis, because it induces endothelial cell proliferation, stimulates angiogenesis and increases vascular permeability, contribute to periodontal healing [42]. In periodontitis patients, VEGF is detected within vascular endothelial cells, neutrophils, plasma cells, and junctional, pocket and gingival epithelium [43]. Various authors reported increased VEGF expression in epithelial cells and endothelial cells in periodontitis-affected gingiva could be an useful marker for periodontal disease [44].

Table 1. Classification of biomarkers [7].

Proteomic biomarkers

Genetic biomarkers

Microbial biomarkers

Other biomarkers

Cystatins,αglucosidase,

Acid phosphatase,

Alkalinephosphatase, Aminopeptidase, Lactoferrin, Translactoferin, IgM, MMP-13, MMP-8, MMP-9, Cathepsin B, Osteonectin, Osteocalcin, Osteopontin, Elastase Platelet-activating factor, Epidermal growth factor, Platelet-derived growth factor, Esterase,

Pyridinoline crosslinked carboxy –terminal telopeptide,

Fibronectin, sIgA (secretory IgA) Gelatinase, IgA, Trypsin, Vascular endothelial growth factor, IgG        

Cathepsin Cgene Mutation,

Collagen gene mutation,

IL-1 polymorphisms,

IL-10 polymorphisms,

Tumor necrosis factor,

Polymorphisms.

Aggregatibacter actinomycetemcomitans,

Campylobacter rectus, Mycoplasmas,

Porphyromonas gingivalis,

Prevotella intermedia, Peptostreptococcus

Micros,

Prevotella nigrescens,

Treponema denticola,

Tannerella forsythia.

Treponema socransky.      

Calcium,

Cortisol,

Hydrogensulphide,

Methylmercaptan,

Pyridine.               

Table 2. Chair side diagnostic kits by using various biomarkers [55].

Assay

Kit

Manufacturer/Supplier

Function

Bacterial enzymes &host enzymes

BANA periodontal test

Ora Tec Corporation Manassas (USA)

It utilizes the BANA test for bacterial trypsin like proteases

Periocheck

CollaGenex Pharmaceuticals, Newtown, PA

Detects presence of neutral proteinases i.e. Collagenase

Perioscan

Oral B Laboratories

Detects enzymatic activity of Aggregatibacter actinomycetemcomitans, T. forsythus, P. gingivalis

Immunological identification

Evalusite

Kodak Eastman Company (Switzerland)

Immunological detection of antigens of Aggregatibacter actinomycetemcomitans, P. intermedia, P. gingivalisusing antibodies (ELISA)

Biochemical identification

Prognostic

Dentsply

Aids in detection of serine proteinases and elastases

Biolise

SLT-Labinstruments, Crailsheim, Ger-many

Aids in detection of elastase

Periogard

Colgate

Detects the presence of AST

Pocket watch

SteriOss®, San Diego, CA, USA

Detects aspartate aminotransferase through colorimetric detection

TOPAS

Affinity Labelling Technologies (USA)

Detects toxins derived from anaerobic metabolism and measures GCF protein level

Genetic biomarkers

Interleukin polymorphisms: A study reported that a “composite” IL-1 genotype consisting of at least one copy of the rarer allele at both an IL-lα and IL-1β loci was associated with severe periodontitis [45]. Karimbux et al. in their meta-analysis reported that IL1A and IL1B genetic variations are significant contributors to chronic periodontitis in Caucasians [46].

Cathepsin c polymorphisms: The underlying causation of Papillon-Lefevre syndrome has been the subject of considerable debate in the literature. Papillon-Lefevre syndrome is caused by mutation in gene coding cathepsin C. This enzyme is expressed at high levels in many immune cells including polymorphonuclear leukocytes and macrophages and their precursors. In addition, it has been found that cathepsin C is expressed in areas of epithelium often affected by hyperkeratosis lesions such as palms, soles, knees and oral keratinized gingiva. But hyperkeratosis present only in homozygous trait.

TNFα gene polymorphism: The TNFα gene is located on chromosome 6 within the major histocompatibility complex (MHC) gene cluster at the location 6p21.3. It is an important mediator in inflammatory reactions and appears to play a central role in the pathogenesis of severe chronic inflammatory diseases. Differences in the rate of production of TNF have been demonstrated and a familial ability to produce higher or lower cytokine levels seems to exist [47]. The TNF synthesis may be influenced by the presence of certain gene polymorphisms [48]. Some consistent results on association of TNFα gene polymorphisms with diseases are reported for infectious diseases particularly malaria. TNFα gene polymorphisms were also investigated in association with periodontitis [49].

CD14 gene polymorphism: The CD14gene is on the chromosome 5 at the location 5q31.1. The production of the sCD14depend on C to T transition at position –159 (also called -260). Subjects with the homozygous TT genotype exhibited significantly higher sCD14 levels which influenced the activation of Th2- to Th1 type cells in the response to bacterial challenge. The -260 CD14 gene polymorphism [50] has been associated with Crohn’s disease and also with periodontitis.

Microbial markers

Although there are almost 600 bacterial species present in subgingival plaque, only few of them are causing periodontal disease in a susceptible host.

A number of specific periodontal pathogens have been implicated in periodontal diseases, including Tanerella forsythensis, Porphyromonas gingivalis, and Treponema denticola. These three organisms are members of the ‘‘red complex’’ of bacteria that are highly implicated in the progression of periodontal diseases. Actinobacillus actinomycetemcomitans has been linked with early-onset forms of periodontal disease and aggressive periodontitis, whereas red complex bacteria are associated with Chronic Periodontitis.

A study conducted to determine whether the presence of bacterial antigens for Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), and Actinobacillus actinomycetemcomitans (A.a) in sub gingival plaque of periodontitis patients after periodontal treatment was associated with progressive alveolar bone loss. Progressive alveolar bone loss was determined using digital subtraction radiography with standardized radiographs taken at baseline and 6 months after treatment and concluded the presence of P. gingivalis in plaque after treatment was significantly associated with progressive bone loss [51].

Other biomarkers

Cortisol: A study evaluated the association of stress, distress, and coping behaviors with periodontal disease and concluded that higher salivary cortisol levels were detected in individuals exhibiting severe periodontitis [52].

Calcium: A study conducted to examine differences in salivary calcium levels in periodontitis patients in comparison to periodontally healthy subjects. The results show that subjects in the high salivary Ca-group had significantly more intact teeth than their pairs in the low salivary Ca group and concluded that an elevated calcium concentration in saliva was characteristic of patients with periodontitis [53].

Volatiles: Volatile sulphur compounds, primarily hydrogen sulfide and methylmercaptan, are associated with oral malodor. Salivary volatiles have been suggested as possible diagnostic markers and contributory factors in periodontal disease. For example, pyridine and Pico lines were found only in subjects with moderate to severe periodontitis. Furthermore, saliva seems to be a useful medium to evaluate oral malodor [54].

Conclusion

In the field of oral disease diagnosis, there has been a steady growing trend during the last two decades to develop tools to monitor periodontitis. From physical measurements such as periodontal probing to sophisticated genetic susceptibility analysis and molecular assays for the detection of biomarkers on the different stages of the disease, substantial improvements have been made on the understanding of the mediators implicated on the initiation and progression of periodontitis. At the same time, this evolutionary process has promoted the discovery of new biomarkers and the development of new therapeutic approaches mainly using host modulation. It is clear that no single marker will fulfill all the criteria necessary for assessment of the clinical state of the periodontium, and future research should be directed at the production of "marker packages". The development of a wide spectrum of marker factors will be a primary goal of periodontal research

References

  1. Socransky SS, Haffajee AD (1992) The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol 63: 322-331. [Crossref]
  2. Zhang L, Henson BS, Camargo PM, Wong DT (2009) The clinical value of salivary biomarkers for periodontal disease. Periodontol 2000 51: 25-37. [Crossref]
  3. The National Institutes of Health Biomarkers Definitions Working Group in 1998.
  4. Reddy S, Kaul S, Prasad MGS, Agnihotri J, Asutkar H, et al. (2011) Biomarkers in Periodontal Diagnosis. What The Future Holds. Int J Clin Dent Sci 2: 76-83.
  5. Guptha M, Nirola A, Bhardwaj SJ (2012) Advances in clinical diagnosis in periodontics. Ind J Dent Scien 4: 114-118.
  6. Chapple IL (2009) Periodontal diagnosis and treatment--where does the future lie? Periodontol 2000 51: 9-24. [Crossref]
  7. Armitage GC (2004) Analysis of gingival crevice fluid and risk of progression of periodontitis. Periodontol 2000 34: 109-119. [Crossref]
  8. Sreedhar A, Shobha Prakash, Sapna N, Santhosh Kumar(2011) Proteomics - the new era of periodontics. J Dent Sci Res 2: 1-5.
  9. Palys MD, Haffajee AD, Socransky SS, Giannobile WV (1998) Relationship between C-telopeptidepyridinoline cross-links (ICTP) and putative periodontal pathogens in periodontitis. J Clin Periodontol 25: 865-871.
  10. Al-Shammari KF, Giannobile WV, Aldredge WA, Iacono VJ, Eber RM, et al. (2001) Effect of non-surgical periodontal therapy on C-telopeptide pyridinoline cross-links (ICTP) and interleukin-1 levels. J Periodontol 72: 1045-1051. [Crossref]
  11. Golub LM, McNamara TF, Ryan ME, Kohut B, Blieden T, et al. (2001) Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis. J Clin Periodontol 28: 146-156. [Crossref]
  12. Kunimatsu K, Mataki S, Tanaka H, Mine N, Kiyoki M, et al. (1993) A cross-sectional study on osteocalcin levels in gingival crevicular fluid from periodontal patients. J Periodontol 64: 865-869. [Crossref]
  13. Nakashima K, Roehrich N, Cimasoni G (1994) Osteocalcin, prostaglandin E2 and alkaline phosphatase in gingival crevicular fluid: their relations to periodontal status.   J Clin Periodontol 21: 327-333. [Crossref]
  14. Chapple IL, Glenwright HD, Matthews JB, Thorpe GH, Lumley PJ (1994) Site-specific alkaline phosphatase levels in gingival crevicular fluid in health and gingivitis: cross-sectional studies. J Clin Periodontol 21: 409-414. [Crossref]
  15. Chapple IL, Socransky SS, Dibart S, Glenwright HD, Matthews JB (1996) Chemiluminescent assay of alkaline phosphatase in human gingival crevicular fluid: investigations with an experimental gingivitis model and studies on the source of the enzyme within crevicular fluid. J Clin Periodontol 23: 587-94.
  16. McCauley LK, Nohutcu RM (2002) Mediators of periodontal osseous destruction and remodeling: principles and implications for diagnosis and therapy. J Periodontol 73: 1377-1391. [Crossref]
  17. Kinney JS, Ramseier CA, Giannobile WV (2007) Oral fluid-based biomarkers of alveolar bone loss in periodontitis. Ann N Y Acad Sci 1098: 230-251. [Crossref]
  18. Rai B, Kharb S, Jain R, Anand SC (2008) Biomarkers of periodontitis in oral fluids. J Oral Sci 50: 53-56. [Crossref]
  19. Mancini S, Romanelli R, Laschinger CA, Overall CM, Sodek J, et al. (1999) Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases. J Periodontol 70: 1292-1302. [Crossref]
  20. Teng YT, Sodek J, McCulloch CA (1992) Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects. J Periodontal Res 27: 544-552. [Crossref]
  21. Gangbar S, Overall CM, Mcculloch CA, Sodek J (1990) Identification of polymorphonuclear leukocyte collagenase and gelatinase activities in mouthrinse samples: Correlation with periodontal disease activity in adult and juvenile periodontitis. J Periodontal Res 25: 257-267.
  22. Over C, Yamalik N, Yavuzyilmaz E, Ersoy F, Eratalay K (1993) Myeloperoxidase activity in peripheral blood, neutrophil crevicular fluid and whole saliva of patients with periodontal disease. J Nihon Univ Sch Dent 35: 235-40.
  23. Kido J, Nakamura T, Kido R, Ohishi K, Yamauchi N, et al. (1999) Calprotectin in gingival crevicular fluid correlates with clinical and biochemical markers of periodontal disease. J Clin Periodontol 26: 653-657. [Crossref]
  24. Sharma CG, Pradeep AR (2006) Gingival crevicular fluid osteopontin levels in periodontal health and disease. J Periodontol 77: 1674-1680. [Crossref]
  25. Kido J, Nakamura T, Asahara Y, Sawa T, Kohri K, et al. (2001) Osteopontin in gingival crevicular fluid. J Periodontal Res 36: 328-333. [Crossref]
  26. Hans S, Mali AM (2012) Estimation and comparison of osteopontin levels in plasma in subjects with healthy periodontium and generalized chronic periodontitis and its assessment after scaling and root planing. J Indian Soc Periodontol 16: 354-357. [Crossref]
  27. Blankenvoorde MF, Henskens YM, van der Weijden GA, van den Keijbus PA, Veerman EC, et al. (1997) Cystatin A in gingival crevicular fluid of periodontal patients. J Periodontal Res 32: 583-588. [Crossref]
  28. Gibbons RJ, Etherden I (1986) Fibronectin-degrading enzymes in saliva and their relation to oral cleanliness. J Periodontal Res 21: 386-395. [Crossref]
  29. Lamberts BL, Pederson ED, Bial JJ, Tombasco PK (1989) Fibronectin levels of unstimulated saliva from naval recruits with and without chronic inflammatory periodontal disease. J Clin Periodontol 16: 342-346. [Crossref]
  30. Markkanen H, Syrjänen SM, Alakuijala P (1986) Salivary IgA, lysozyme and beta 2-microglobulin in periodontal disease. Scand J Dent Res 94: 115-120. [Crossref]
  31. Jalil RA, Ashley FP, Wilson (1993) Concentration of thiocyanate, hypothiocyanite, ‘free’ and ‘total’ lysozyme, lactoferrin and secretory Ig A in resting and stimulated whole saliva of children aged 12-14 yrs and the relationship with plaque accumulation and gingivitis. J Periodontal Res 28: 130-136.
  32. Delacroix DL, Dive C, Rambaud JC, Vaerman JP (1982) IgA subclasses in various secretions and in serum. Immunology 47: 383-385. [Crossref]
  33. Lindström FD, Folke LE (1973) Salivary IgA in periodontal disease. Acta Odontol Scand 31: 31-34. [Crossref]
  34. Eggert FM, Maenz L, Tam YC (1987) Measuring the interaction of human secretory glycoproteins with oral bacteria. J Dent Res 66: 610-612. [Crossref]
  35. Sandholm L, Tolo K, Olsen I (1987) Salivary IgG, a parameter of periodontal disease activity? High responders to Actinobacillus actinomycetemcomitans Y4 in juvenile and adult periodontitis. J Clin Periodontol 14: 289-294. [Crossref]
  36. Gregory RL, Kim DE, Kindle JC, Hobbs LC, Lloyd DR (1992) Immunoglobulin-degrading enzymes in localized juvenile periodontitis. J Periodontal Res 27: 176-183. [Crossref]
  37. Garito ML, Prihoda TJ, McManus LM (1995) Salivary PAF levels correlate with the severity of periodontal inflammation. J Dent Res 74: 1048-1056. [Crossref]
  38. Rasch MS, Mealey BL, Prihoda TJ, Woodard DS, McManus LM (1995) The effect of initial periodontal therapy on salivary platelet-activating factor levels in chronic adult periodontitis. J Periodontol 66: 613-623. [Crossref]
  39. Hormia M, Thesleff I, Perheentupa J, Pesonen K, Saxén L (1993) Increased rate of salivary epidermal growth factor secretion in patients with juvenile periodontitis. Scand J Dent Res 101: 138-144. [Crossref]
  40. Giannobile WV, Hernandez RA, Finkelman RD, Ryan S, Kiritsy CP, et al. (1996) Comparative effects of platelet-derived growth factor-BB and insulin-like growth factor-I, individually and in combination, on periodontal regeneration in Macaca fascicularis. J Periodontal Res 31: 301-312. [Crossref]
  41. Pinheiro ML, Feres-Filho EJ, Graves DT, Takiya CM, Elsas MI, et al. (2003) Quantification and localization of platelet-derived growth factor in gingiva of periodontitis patients. J Periodontol 74: 323-328. [Crossref]
  42. Ferrara N (2009) Vascular endothelial growth factor. Arterioscler Thromb Vasc Biol 29: 789-791. [Crossref]
  43. Booth V, Young S, Cruchley A, Taichman NS, Paleolog E (1998) Vascular endothelial growth factor in human periodontal disease. J Periodontal Res 33: 491-499. [Crossref]
  44. Giannobile WV, Al-Shammari KF, Sarment DP (2003) Matrix molecules and growth factors as indicators of periodontal disease activity. Periodontol 2000 31: 125-134. [Crossref]
  45. Kornman KS, Page RC, Tonetti MS (1997) The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000 14: 33-53. [Crossref]
  46. Karimbux NY, Saraiya VM, Elangovan S, Allareddy V, Kinnunen T, et al. (2012) Interleukin-1 gene polymorphisms and chronic periodontitis in adult whites: a systematic review and meta-analysis. J Periodontol 83: 1407-1419. [Crossref]
  47. Pociot For (1993) Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-α and TNF-β by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. Eur J Immunol 23: 224–231.
  48. Duff (1994) Molecular genetics of cytokines. In: Thomson (ed.) the cytokine handbook 2nd edition: pg 21-30.
  49. Bayley JP, Ottenhoff TH, Verweij CL (2004) Is there a future for TNF promoter polymorphisms? Genes Immun 5: 315-329. [Crossref]
  50. Klein W, Tromm A, Griga T, Fricke H, Folwaczny C, et al. (2002) A polymorphism in the CD14 gene is associated with Crohn disease. Scand J Gastroenterol 37: 189-191. [Crossref]
  51. Chaves ES, Jeffcoat MK, Ryerson CC, Snyder B (2000) Persistent bacterial colonization of Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans in periodontitis and its association with alveolar bone loss after 6 months of therapy. J Clin Periodontol 27: 897–903.
  52. Genco RJ, Ho AW, Kopman J, Grossi SG, Dunford RG, et al. (1998) Models to evaluate the role of stress in periodontal disease. Ann Periodontol 3: 288-302. [Crossref]
  53. Sewón L, Mäkelä M (1990) A study of the possible correlation of high salivary calcium levels with periodontal and dental conditions in young adults. Arch Oral Biol 35 Suppl: 211S-212S. [Crossref]
  54. Marc Quiryen and Daniel van Steenberghe (2007) Oral Malodor. In: Carranza FA, Newman MG, and Takei HH. Carranza’s Clinical Periodontology 10th edition. Philadelphia: Saunders: 330-342.
  55. Sachin Malaga (2012) Chairside diagnostic test kits in periodontics - A review. Int Arab J Dent 3: 101-102.

Editorial Information

Editor-in-Chief

JON B. SUZUKI
Temple University

Article Type

Review Article

Publication history

Received date: March 28, 2015
Accepted date: April 25, 2015
Published date: April 28, 2015

Copyright

©2015 Pavan Kumar A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Pavan Kumar A, Jagdish Reddy G, Raja babu P (2015). Biomarkers in periodontal disease. Dent Oral Craniofac Res 1: doi: 10.15761/DOCR.1000111

Corresponding author

Pavan Kumar A

Kamineni Institute of dental sciences, India, Tel: 9030239565.

E-mail : pavankumar2524@gmail.com

Table 1. Classification of biomarkers [7].

Proteomic biomarkers

Genetic biomarkers

Microbial biomarkers

Other biomarkers

Cystatins,αglucosidase,

Acid phosphatase,

Alkalinephosphatase, Aminopeptidase, Lactoferrin, Translactoferin, IgM, MMP-13, MMP-8, MMP-9, Cathepsin B, Osteonectin, Osteocalcin, Osteopontin, Elastase Platelet-activating factor, Epidermal growth factor, Platelet-derived growth factor, Esterase,

Pyridinoline crosslinked carboxy –terminal telopeptide,

Fibronectin, sIgA (secretory IgA) Gelatinase, IgA, Trypsin, Vascular endothelial growth factor, IgG        

Cathepsin Cgene Mutation,

Collagen gene mutation,

IL-1 polymorphisms,

IL-10 polymorphisms,

Tumor necrosis factor,

Polymorphisms.

Aggregatibacter actinomycetemcomitans,

Campylobacter rectus, Mycoplasmas,

Porphyromonas gingivalis,

Prevotella intermedia, Peptostreptococcus

Micros,

Prevotella nigrescens,

Treponema denticola,

Tannerella forsythia.

Treponema socransky.      

Calcium,

Cortisol,

Hydrogensulphide,

Methylmercaptan,

Pyridine.               

Table 2. Chair side diagnostic kits by using various biomarkers [55].

Assay

Kit

Manufacturer/Supplier

Function

Bacterial enzymes &host enzymes

BANA periodontal test

Ora Tec Corporation Manassas (USA)

It utilizes the BANA test for bacterial trypsin like proteases

Periocheck

CollaGenex Pharmaceuticals, Newtown, PA

Detects presence of neutral proteinases i.e. Collagenase

Perioscan

Oral B Laboratories

Detects enzymatic activity of Aggregatibacter actinomycetemcomitans, T. forsythus, P. gingivalis

Immunological identification

Evalusite

Kodak Eastman Company (Switzerland)

Immunological detection of antigens of Aggregatibacter actinomycetemcomitans, P. intermedia, P. gingivalisusing antibodies (ELISA)

Biochemical identification

Prognostic

Dentsply

Aids in detection of serine proteinases and elastases

Biolise

SLT-Labinstruments, Crailsheim, Ger-many

Aids in detection of elastase

Periogard

Colgate

Detects the presence of AST

Pocket watch

SteriOss®, San Diego, CA, USA

Detects aspartate aminotransferase through colorimetric detection

TOPAS

Affinity Labelling Technologies (USA)

Detects toxins derived from anaerobic metabolism and measures GCF protein level