The Role of Porphyromonas gingivalis in Oral Biofilm: Pathophysiology in Chronic Periodontitis

Pratiwi Soesilawati; Nur Imamatul Ummah; Sesaria Junita Mega Rahma Syahnia; Niken Luthfiyya Arini; Aqsa Sjuhada Oki

doi:10.52711/0974-360X.2023.00289

Research Journal of Pharmacy and Technology

ISSN

0974-360X (Online)
0974-3618 (Print)

Submit Article

The Role of Porphyromonas gingivalis in Oral Biofilm: Pathophysiology in Chronic Periodontitis

Author(s): Pratiwi Soesilawati, Nur Imamatul Ummah, Sesaria Junita Mega Rahma Syahnia, Niken Luthfiyya Arini, Aqsa Sjuhada Oki

Email(s): pratiwi-s@fkg.unair.ac.id

DOI: 10.52711/0974-360X.2023.00289

Address: Pratiwi Soesilawati2*, Nur Imamatul Ummah1, Sesaria Junita Mega Rahma Syahnia1, Niken Luthfiyya Arini1, Aqsa Sjuhada Oki2
1Undergraduate Student, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.
2Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.
*Corresponding Author

Published In: Volume - 16, Issue - 4, Year - 2023

View HTML

View PDF

ABSTRACT:
Periodontitis is a destructive inflammatory disease caused by a specific microorganism causing progressive damage to areas, especially the alveolar bone and periodontal ligament. Clinical manifestations of periodontitis are tooth mobility, pocket formation, and loss of attachment. Periodontitis is divided into two groups, namely aggressive and chronic periodontitis. The prevalence of chronic periodontitis in the world is around 50%. Meanwhile, the prevalence of chronic periodontitis in Indonesia, according to Riskesdas 2018 is 67.8%. Porphyromonas gingivalis is a bacterium that causes chronic periodontitis, which can form biofilm plaque and cause damage to periodontal tissue resulting in tooth loss. The formation of biofilm plaques due to accumulation of opportunistic bacterial species accompanied by increased gram-negative bacterial. These changes in composition affect the host's immune response so that periodontitis develops into a chronic inflammatory condition. Therefore, we conducted a literature search to analyze the effect of oral biofilms on chronic periodontitis.

Keywords:

Cite this article:
Pratiwi Soesilawati, Nur Imamatul Ummah, Sesaria Junita Mega Rahma Syahnia, Niken Luthfiyya Arini, Aqsa Sjuhada Oki. The Role of Porphyromonas gingivalis in Oral Biofilm: Pathophysiology in Chronic Periodontitis. Research Journal of Pharmacy and Technology 2023; 16(4):1754-0. doi: 10.52711/0974-360X.2023.00289

Cite(Electronic):
Pratiwi Soesilawati, Nur Imamatul Ummah, Sesaria Junita Mega Rahma Syahnia, Niken Luthfiyya Arini, Aqsa Sjuhada Oki. The Role of Porphyromonas gingivalis in Oral Biofilm: Pathophysiology in Chronic Periodontitis. Research Journal of Pharmacy and Technology 2023; 16(4):1754-0. doi: 10.52711/0974-360X.2023.00289 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-4-37

REFERENCES:
1.    Dorland. Kamus Saku Kedokteran Dorland. Elsevier (Singapore) Pte. Ltd. 2020;
2.    Andriani I. Efektivitas Antara Scaling Root Planing (Srp) Dengan dan Tanpa Pemberian Ciprofloxacin Per Oral Pada Penderita Periodontitis. 2012;1(2):doi.org/10.18196/di.v1i2.534.
3.    Surya L. Sutiawan B. Hubungan Faktor Lokal, Faktor Sistemik dan Faktor Perilaku Terhadap Kejadian Penyakit Periodontal Di Indonesia (Analisis Riskesdas). 2019;8(2):57–66.doi.org/10.35856/mdj.v8i2.271.
4.    Newman MG. Takei H. Carranza FA. Klokkevold PR. Carranza’s Clinical Periodontology. Saunders, St. Louis, Mo. 2006;
5.    Penmetsa GS. Bhavana P. Arunbhupati P. Meghana K. Kausalya P. Venkatalakshmi M. Comparative Evaluation of the Clinical Efficacy of 3% Satranidazole and 1% Ornidazole (OrnigreatTM) Gel through Local Drug Delivery System in the Treatment of Chronic Periodontitis. Research Journal of Pharmacy and Technology. 2020;13(8):3675–3680.doi.org/10.5958/0974-360X.2020.00650.2.
6.    Kadiyala V. Savitha G. Assessment of Gamma Glutamyl Transferase in Chronic Periodontitis. Research Journal of Pharmacy and Technology. 2018;11(11):5083–5085.doi.org/10.5958/0974-360X.2018.00927.7.
7.    Govindaraj J. Govindaraj K. Vidyarekha U. Padmavathy K. Antiinflammatory Effect of Proanthocyanidins in Experimental Periodontitis in Rats. Research Journal of Pharmacy and Technology. 2019;12(10):4747–4751.doi.org/10.5958/0974-360X.2019.00818.7.
8.    Rahmania R. Epsilawati L. Rusminah N. Densitas Tulang Alveolar pada Penderita Periodontitis Kronis dan Periodontitis Agresif Melalui Radiografi. 2019;3(2):7–10.doi.org/10.32793/jrdi.v3i2.484.
9.    Krishnan M. Krishnan P. Chandrasekaran S. Panishankar KH. Subashini N. Prevalence of Periodontopathic Bacteria in the Subgingival Plaque of a South Indian Population with Periodontitis. 2012;6747–6752.
10.    Armitage GC. Periodontal Diagnoses and Classification of Periodontal Diseases. 2004;349–21.doi.org/10.1046/j.0906-6713.2002.003421.x.
11.    Reynolds MA. Modifiable Risk Factors in Periodontitis: At the Intersection of Aging and Disease. 2014;64(1):7–19.doi.org/10.1111/prd.12047.
12.    Swathi KV. Maragathavalli G. Erosive Oral Lichen Planus-A Case Report. Research Journal of Pharmacy and Technology. 2019;12(6):3007–3011.doi.org/10.5958/0974-360X.2019.00508.0.
13.    Lombardi T. Bernardello F. Berton F. Porrelli D. Rapani A. Camurri Piloni A. et al. Efficacy of Alveolar Ridge Preservation after Maxillary Molar Extraction in Reducing Crestal Bone Resorption and Sinus Pneumatization: A Multicenter Prospective Case-Control Study. Hindawi. 2018;2018e9352130.doi.org/10.1155/2018/9352130.
14.    Cervino G. Romeo U. Lauritano F. Bramanti E. Fiorillo L. D’Amico C. et al. Analysis of OSSTEM ® Dental Implant Structural Components: Evaluation of Different Direction Dynamic Loads. 2018;12219–229.doi.org/10.2174/1874210601812010219.
15.    Purbowati R. Hubungan Biofilm dengan Infeksi: Implikasi pada Kesehatan Masyarakat dan Strategi Mengontrolnya. 2018;5(1):1.doi.org/10.30742/jikw.v5i1.1.
16.    Jamal M. Tasneem U. Hussain T. Andleeb S. Bacterial Biofilm: Its Composition, Formation and Role in Human Infections. Research and Reviews. 2015;4(3):
17.    Veerachamy S. Yarlagadda T. Manivasagam G. Yarlagadda P. Bacterial Adherence and Biofilm Formation on Medical Implants: A Review. 2014;2281083–1099.doi.org/10.1177/0954411914556137.
18.    Berger D. Rakhamimova, A. Pollack, A. Loewy, Z. Oral Biofilms: Development, Control, and Analysis. 2018;7(3):E24.doi.org/10.3390/ht7030024.
19.    Da Cunda P. Iribarnegaray V. Papa-Ezdra R. Bado I. González MJ. Zunino P. et al. Characterization of the Different Stages of Biofilm Formation and Antibiotic Susceptibility in a Clinical Acinetobacter Baumannii Strain. 2020;26(6):569–575.doi.org/10.1089/mdr.2019.0145.
20.    Vasudevan R. Biofilms: Microbial Cities of Scientific Significance. 2014;1(3):10.15406/jmen.2014.01.00014.
21.    Hollman B. Perkins M. Walsh D. Biofilms and Their Role in Pathogenesis. 2020;
22.    Yan S. Wu G. Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas Aeruginosa? 2019;101582.doi.org/10.3389/fmicb.2019.01582.
23.    Abedon ST. Ecology of Anti-Biofilm Agents II: Bacteriophage Exploitation and Biocontrol of Biofilm Bacteria. 2015;8(3):559–589.doi.org/10.3390/ph8030559.
24.    Mian K. Investigation of Bacterial Biofilm Sample Taken from Fresh Water and Soil and Some Antibiofilm Approaches. 2021;5.
25.    Sriram N. S G. P G. Microbiological Speciation of Aerobic Bacteria in Patients Undergoing Treatment for Oral Malignancy. Research Journal of Pharmacy and Technology. 2018;11(7):2721–2723.doi.org/10.5958/0974-360X.2018.00502.4.
26.    Vaishali M. Kumar RP. Nutritional Counselling in Oral Health. Research Journal of Pharmacy and Technology. 2018;11(10):4749–4750.doi.org/10.5958/0974-360X.2018.00865.X.
27.    Hajishengallis G. Periodontitis: from Microbial Immune Subversion to Systemic Inflammation. 2015;15(1):30–44.doi.org/10.1038/nri3785.
28.    He J. Li Y. Cao Y. Xue J. Zhou X. The Oral Microbiome Diversity and Its Relation to Human Diseases. 2015;60(1):69–80.doi.org/10.1007/s12223-014-0342-2.
29.    Jadhav PA. Yadav AV. Polymeric Nanosuspension Loaded Oral Thin Films of Flurbiprofen: Design, Development and In Vitro Evaluation. Research Journal of Pharmacy and Technology. 2020;13(4):1905–1910.doi.org/10.5958/0974-360X.2020.00343.1.
30.    Pargi PM. Purohit BM. Hadiyel LN. Roy T. Mukhopadhyay D. Ghosh S. et al. Metoprolol Induced Oral Lichen Planus in An Adult Female Patient – A Case Report. Research Journal of Pharmacy and Technology. 2020;13(9):4274–4276.doi.org/10.5958/0974-360X.2020.00754.4.
31.    Jose J. Ashwini PB. Nayak P. Charyulu RN. Oral Dispersible Films, Novel Technology for the Delivery of Drugs. Research Journal of Pharmacy and Technology. 2019;12(1):425–428.doi.org/10.5958/0974-360X.2019.00077.5.
32.    Hajishengallis G. Lamont RJ. Beyond the Red Complex and into More Complexity: The Polymicrobial Synergy and Dysbiosis (PSD) Model of Periodontal Disease Etiology. 2012;27(6):409–419.doi.org/10.1111/j.2041-1014.2012.00663.x.
33.    Quamilla N. Stres dan Kejadian Periodontitis (Kajian Literatur). 2016;8.
34.    Hendrawati H. Agustha HN. Sari R. Topical Application of Snail Mucin Gel Enhances the Number of Osteoblasts in Periodontitis Rat Model. 2019;52(2):61–65.doi.org/10.20473/j.djmkg.v52.i2.p61-65.
35.    Fatikhah N. Yubiliana G. Rinawan FR. Electronic Application for Oral Health School Programme Enhances the Quality of the Information in Dental Health Data Records. 2020;53(4):206–211.doi.org/10.20473/j.djmkg.v53.i4.p206-211.
36.    Thiele S. Rauner M. Goes P. Recent Advances in Periodontitis, a Prototypic Osteo-Immunological Disease. AME Publishing Company. 2018;3(0):
37.    Kinane DF. Stathopoulou PG. Papapanou PN. Periodontal Diseases. 2017;317038.doi.org/10.1038/nrdp.2017.38.
38.    Nield-Gehrig, JS. Willmann, DE. Foundations of Periodontics for the Dental Hygienist. Wolters Kluwer, Lippincot. Williams & Wilkins. 2003;
39.    Carranza FA. Camargo P. Periodontal Pocket. In : Newman MG, Takei HH, Klokkevold PR, Carranza FA, Editors. Carranza’s Clinical Periodontology. Saunders Elsevier, Philadelphia. 2006;
40.    Shetty SS. Quays DR. John J. Yee NS. Appu D. a/p.Tze LM. Chuen TS. et al. Effect of Oil Pulling on Oral Health- A Microbiological Study. Research Journal of Pharmacy and Technology. 2019;12(1):01–04.doi.org/10.5958/0974-360X.2019.00001.5.
41.    Meenambiga SS. Rajagopal K. Shevalkar M. Endophytic Fungi, A Novel Source in the Treatment of Oral Infections. Research Journal of Pharmacy and Technology. 2020;13(6):2936–2942.doi.org/10.5958/0974-360X.2020.00520.X.
42.    Preethi PR. Jayashri P. Influence of Naturally Occurring Phytochemicals on Oral Health. Research Journal of Pharmacy and Technology. 2019;12(8):3979–3983.doi.org/10.5958/0974-360X.2019.00685.1.
43.    Pranati T. Anitha R. Rajeshkumar S. Lakshmi T. Preparation of Silver Nanoparticles Using Nutmeg Oleoresin and Its Antimicrobial Activity against Oral Pathogens. Research Journal of Pharmacy and Technology. 2019;12(6):2799–2803.doi.org/10.5958/0974-360X.2019.00471.2.
44.    Lavanya E. Ganapathy D. Sheeba S. Effect of Removable Partial Denture on Periodontal Health of Abutments. Research Journal of Pharmacy and Technology. 2018;11(6):2587–2590.doi.org/10.5958/0974-360X.2018.00478.X.
45.    Aide MI. Mental Health. 2008;12–15.
46.    Bonneville M. O’Brien RL. Born WK. Gammadelta T Cell Effector Functions: A Blend of Innate Programming and Acquired Plasticity. 2010;10(7):467–478.doi.org/10.1038/nri2781.
47.    Valdor R. Macian F. Induction and Stability of the Anergic Phenotype in T Cells. 2013;25(4):313–320.doi.org/10.1016/j.smim.2013.10.010.
48.    Dutzan N. Konkel JE. Greenwell-Wild T. Moutsopoulos NM. Characterization of the Human Immune Cell Network at the Gingival Barrier. 2016;9 (5):1163–1172.doi.org/10.1038/mi.2015.136.
49.    Zhu J. Paul WE. CD4 T Cells: Fates, Functions, and Faults. 2008;112 (5):1557–156910.1182/blood-2008-05-078154.
50.    Campbell L. Millhouse E. Malcolm J. Culshaw S. T Cells, Teeth and Tissue Destruction - What Do T Cells Do in Periodontal Disease? 2016;doi.org/10.1111/omi.12144.
51.    Chen ML. Sundrud MS. Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases. 2016;22(5):1157–1167.doi.org/10.1097/MIB.0000000000000714.
52.    Jarry CR. Duarte PM. Freitas FF. de Macedo CG. Clemente-Napimoga JT. Saba-Chujfi E. et al. Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT), a Novel Osteoclast Activator, in Chronic Periodontitis. 2013;74(7):861–866.doi.org/10.1016/j.humimm.2013.04.013.
53.    Di Benedetto A. Gigante I. Colucci S. Grano M. Periodontal Disease: Linking the Primary Inflammation to Bone Loss. 2013;2013503754.doi.org/10.1155/2013/503754.
54.    Park YD. Kim YS. Jung YM. Lee SI. Lee YM. Bang JB. et al. Porphyromonas gingivalis Lipopolysaccharide Regulates Interleukin (IL)-17 and IL-23 Expression via SIRT1 Modulation in Human Periodontal Ligament Cells. 2012;60(1):284–293.doi.org/10.1016/j.cyto.2012.05.021.
55.    Koide M. Kobayashi Y. Ninomiya T. Nakamura M. Yasuda H. Arai Y. et al. Osteoprotegerin-Deficient Male Mice as a Model for Severe Alveolar Bone Loss: Comparison with RANKL-Overexpressing Transgenic Male Mice. 2013;154(2):773–782.doi.org/10.1210/en.2012-1928.
56.    Kajimoto N. de C. de Paiva Buischi Y. Loomer PM. Bromage TG. Ervolino E. et al. Adjuvant Therapy with 1% Alendronate Gel for Experimental Periodontitis Treatment in Rats. 2020;51.doi.org/10.5051/jpis.2100700035.
57.    Metzger CE. Narayanan A. Zawieja DC. Bloomfield SA. Inflammatory Bowel Disease in a Rodent Model Alters Osteocyte Protein Levels Controlling Bone Turnover. 2017;32(4):802–813.doi.org/10.1002/jbmr.3027.
58.    Xiao W. Li S. Pacios S. Wang Y. Graves DT. Bone Remodeling Under Pathological Conditions. 2016;1817–27.doi.org/10.1159/000351896.
59.    Costa LC. Fonseca MA. da.Pinheiro A. da R. Aguiar TR. da S. Machado AN. et al. Chronic Periodontitis and RANKL/OPG Ratio in Peri-Implant Mucosae Inflammation. 2018;29(1):14–22.doi.org/10.1590/0103-6440201801241.
60.    Carcuac O. Berglundh T. Composition of Human Peri-Implantitis and Periodontitis Lesions. 2014;93(11):1083–1088.doi.org/10.1177/0022034514551754.
61.    Moutsopoulos NM. Zerbe CS. Wild T. Dutzan N. Brenchley L. DiPasquale G. et al. Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. 2017;376(12):1141–1146.doi.org/10.1056/NEJMoa1612197.
62.    Carbone F. Crowe LA. Roth A. Burger F. Lenglet S. Braunersreuther V. et al. Treatment with Anti-RANKL Antibody Reduces Infarct Size and Attenuates Dysfunction Impacting on Neutrophil-Mediated Injury. 2016;9482–94.doi.org/10.1016/j.yjmcc.2016.03.013.
63.    Nicu EA. Loos BG. Polymorphonuclear Neutrophils in Periodontitis and Their Possible Modulation as a Therapeutic Approach. 2016;71(1):140–163.doi.org/10.1111/prd.12113.
64.    Malcolm J. Awang RA. Oliver-Bell J. Butcher JP. Campbell L. Adrados Planell A. et al. IL-33 Exacerbates Periodontal Disease through Induction of RANKL. 2015;94(7):968–97510.1177/0022034515577815.
65.    Steinmetz O. Hoch S. Avniel-Polak S. Gavish K. Eli-Berchoer L. Wilensky A. et al. CX3CR1hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection–Driven Bone Resorption. 2016;213(9):1505–1515.doi.org/10.1093/infdis/jiv763.
66.    Yoshihara-Hirata C. Yamashiro K. Yamamoto T. Aoyagi H. Ideguchi H. Kawamura M. et al. Anti-HMGB1 Neutralizing Antibody Attenuates Periodontal Inflammation and Bone Resorption in a Murine Periodontitis Model. 2018;86(5):e00111-18.doi.org/10.1128/IAI.00111-18.
67.    Kobayashi T. Yokoyama T. Ito S. Kobayashi D. Yamagata A. Okada M. et al. Periodontal and Serum Protein Profiles in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitor Adalimumab. 2014;85(11):1480–1488.doi.org/10.1902/jop.2014.140194.
68.    Schett G. Neurath MF. Resolution of Chronic Inflammatory Disease: Universal and Tissue-Specific Concepts. 2018;9(1):3261.doi.org/10.1038/s41467-018-05800-6.
69.    Lam RS. O’Brien-Simpson NM. Hamilton JA. Lenzo JC. Holden JA. Brammar GC. et al. GM-CSF and UPA Are Required for Porphyromonas Gingivalis-Induced Alveolar Bone Loss in a Mouse Periodontitis Model. 2015;93(8):705–715.doi.org/10.1038/icb.2015.25.
70.    Fleetwood AJ. O’Brien-Simpson NM. Veith PD. Lam RS. Achuthan A. Cook AD. et al. Porphyromonas gingivalis-Derived RgpA-Kgp Complex Activates the Macrophage Urokinase Plasminogen Activator System: Implications for Periodontitis. 2015;290 (26):16031–16042.doi.org/10.1074/jbc.M115.645572.
71.    Wilensky A. Polak D. Houri-Haddad Y. Shapira L. The Role of RgpA in the Pathogenicity of Porphyromonas gingivalis in the Murine Periodontitis Model. 2013;40(10):924–932.doi.org/10.1111/jcpe.12139.
72.    Wong DM. Tam V. Lam R. Walsh KA. Tatarczuch L. Pagel CN. et al. Protease-Activated Receptor 2 Has Pivotal Roles in Cellular Mechanisms Involved in Experimental Periodontitis. 2010;78(2):629–638.doi.org/10.1128/IAI.01019-09.
73.    Francis N. Ayodele BA. O’Brien-Simpson NM. Birchmeier W. Pike RN. Pagel CN. et al. Keratinocyte-Specific Ablation of Protease-Activated Receptor 2 Prevents Gingival Inflammation and Bone Loss in a Mouse Model of Periodontal Disease. 2018;20(11):e12891.doi.org/10.1111/cmi.12891.
74.    Maekawa T. Abe T. Hajishengallis E. Hosur KB. DeAngelis RA. Ricklin D. et al. Genetic and Intervention Studies Implicating Complement C3 as a Major Target for the Treatment of Periodontitis. 2014;192(12):6020–6027.doi.org/10.4049/jimmunol.1400569.
75.    Graves DT. Alshabab A. Albiero ML. Mattos M. Corrêa JD. Chen S. et al. Osteocytes Play an Important Role in Experimental Periodontitis in Healthy and Diabetic Mice through Expression of RANKL. 2018;45(3):285–29210.1111/jcpe.12851.
76.    Pacios S. Xiao W. Mattos M. Lim J. Tarapore R. Alsadun S. et al. Graves D. Osteoblast Lineage Cells Play an Essential Role in Periodontal Bone Loss Through Activation of Nuclear Factor-Kappa B. 2015;516694.doi.org/10.1038/srep16694.
77.    Yang CY. Jeon HH. Alshabab A. Lee YJ. Chung CH. Graves DT. RANKL Deletion in Periodontal Ligament and Bone Lining Cells Blocks Orthodontic Tooth Movement. 2018;10(1):3.doi.org/10.1038/s41368-017-0004-8.
78.    Danks L. Komatsu N. Guerrini MM. Sawa S. Armaka M. Kollias G. et al. RANKL Expressed on Synovial Fibroblasts Is Primarily Responsible for Bone Erosions during Joint Inflammation. 2016;75 (6):1187–1195.doi.org/10.1136/annrheumdis-2014-207137.

REFERENCES:

1. Dorland. Kamus Saku Kedokteran Dorland. Elsevier (Singapore) Pte. Ltd. 2020;

2. Andriani I. Efektivitas Antara Scaling Root Planing (Srp) Dengan dan Tanpa Pemberian Ciprofloxacin Per Oral Pada Penderita Periodontitis. 2012;1(2):doi.org/10.18196/di.v1i2.534.

3. Surya L. Sutiawan B. Hubungan Faktor Lokal, Faktor Sistemik dan Faktor Perilaku Terhadap Kejadian Penyakit Periodontal Di Indonesia (Analisis Riskesdas). 2019;8(2):57–66.doi.org/10.35856/mdj.v8i2.271.

4. Newman MG. Takei H. Carranza FA. Klokkevold PR. Carranza’s Clinical Periodontology. Saunders, St. Louis, Mo. 2006;

5. Penmetsa GS. Bhavana P. Arunbhupati P. Meghana K. Kausalya P. Venkatalakshmi M. Comparative Evaluation of the Clinical Efficacy of 3% Satranidazole and 1% Ornidazole (OrnigreatTM) Gel through Local Drug Delivery System in the Treatment of Chronic Periodontitis. Research Journal of Pharmacy and Technology. 2020;13(8):3675–3680.doi.org/10.5958/0974-360X.2020.00650.2.

6. Kadiyala V. Savitha G. Assessment of Gamma Glutamyl Transferase in Chronic Periodontitis. Research Journal of Pharmacy and Technology. 2018;11(11):5083–5085.doi.org/10.5958/0974-360X.2018.00927.7.

7. Govindaraj J. Govindaraj K. Vidyarekha U. Padmavathy K. Antiinflammatory Effect of Proanthocyanidins in Experimental Periodontitis in Rats. Research Journal of Pharmacy and Technology. 2019;12(10):4747–4751.doi.org/10.5958/0974-360X.2019.00818.7.

8. Rahmania R. Epsilawati L. Rusminah N. Densitas Tulang Alveolar pada Penderita Periodontitis Kronis dan Periodontitis Agresif Melalui Radiografi. 2019;3(2):7–10.doi.org/10.32793/jrdi.v3i2.484.

9. Krishnan M. Krishnan P. Chandrasekaran S. Panishankar KH. Subashini N. Prevalence of Periodontopathic Bacteria in the Subgingival Plaque of a South Indian Population with Periodontitis. 2012;6747–6752.

10. Armitage GC. Periodontal Diagnoses and Classification of Periodontal Diseases. 2004;349–21.doi.org/10.1046/j.0906-6713.2002.003421.x.

11. Reynolds MA. Modifiable Risk Factors in Periodontitis: At the Intersection of Aging and Disease. 2014;64(1):7–19.doi.org/10.1111/prd.12047.

12. Swathi KV. Maragathavalli G. Erosive Oral Lichen Planus-A Case Report. Research Journal of Pharmacy and Technology. 2019;12(6):3007–3011.doi.org/10.5958/0974-360X.2019.00508.0.

13. Lombardi T. Bernardello F. Berton F. Porrelli D. Rapani A. Camurri Piloni A. et al. Efficacy of Alveolar Ridge Preservation after Maxillary Molar Extraction in Reducing Crestal Bone Resorption and Sinus Pneumatization: A Multicenter Prospective Case-Control Study. Hindawi. 2018;2018e9352130.doi.org/10.1155/2018/9352130.

14. Cervino G. Romeo U. Lauritano F. Bramanti E. Fiorillo L. D’Amico C. et al. Analysis of OSSTEM ® Dental Implant Structural Components: Evaluation of Different Direction Dynamic Loads. 2018;12219–229.doi.org/10.2174/1874210601812010219.

15. Purbowati R. Hubungan Biofilm dengan Infeksi: Implikasi pada Kesehatan Masyarakat dan Strategi Mengontrolnya. 2018;5(1):1.doi.org/10.30742/jikw.v5i1.1.

16. Jamal M. Tasneem U. Hussain T. Andleeb S. Bacterial Biofilm: Its Composition, Formation and Role in Human Infections. Research and Reviews. 2015;4(3):

17. Veerachamy S. Yarlagadda T. Manivasagam G. Yarlagadda P. Bacterial Adherence and Biofilm Formation on Medical Implants: A Review. 2014;2281083–1099.doi.org/10.1177/0954411914556137.

18. Berger D. Rakhamimova, A. Pollack, A. Loewy, Z. Oral Biofilms: Development, Control, and Analysis. 2018;7(3):E24.doi.org/10.3390/ht7030024.

19. Da Cunda P. Iribarnegaray V. Papa-Ezdra R. Bado I. González MJ. Zunino P. et al. Characterization of the Different Stages of Biofilm Formation and Antibiotic Susceptibility in a Clinical Acinetobacter Baumannii Strain. 2020;26(6):569–575.doi.org/10.1089/mdr.2019.0145.

20. Vasudevan R. Biofilms: Microbial Cities of Scientific Significance. 2014;1(3):10.15406/jmen.2014.01.00014.

21. Hollman B. Perkins M. Walsh D. Biofilms and Their Role in Pathogenesis. 2020;

22. Yan S. Wu G. Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas Aeruginosa? 2019;101582.doi.org/10.3389/fmicb.2019.01582.

23. Abedon ST. Ecology of Anti-Biofilm Agents II: Bacteriophage Exploitation and Biocontrol of Biofilm Bacteria. 2015;8(3):559–589.doi.org/10.3390/ph8030559.

24. Mian K. Investigation of Bacterial Biofilm Sample Taken from Fresh Water and Soil and Some Antibiofilm Approaches. 2021;5.

25. Sriram N. S G. P G. Microbiological Speciation of Aerobic Bacteria in Patients Undergoing Treatment for Oral Malignancy. Research Journal of Pharmacy and Technology. 2018;11(7):2721–2723.doi.org/10.5958/0974-360X.2018.00502.4.

26. Vaishali M. Kumar RP. Nutritional Counselling in Oral Health. Research Journal of Pharmacy and Technology. 2018;11(10):4749–4750.doi.org/10.5958/0974-360X.2018.00865.X.

27. Hajishengallis G. Periodontitis: from Microbial Immune Subversion to Systemic Inflammation. 2015;15(1):30–44.doi.org/10.1038/nri3785.

28. He J. Li Y. Cao Y. Xue J. Zhou X. The Oral Microbiome Diversity and Its Relation to Human Diseases. 2015;60(1):69–80.doi.org/10.1007/s12223-014-0342-2.

29. Jadhav PA. Yadav AV. Polymeric Nanosuspension Loaded Oral Thin Films of Flurbiprofen: Design, Development and In Vitro Evaluation. Research Journal of Pharmacy and Technology. 2020;13(4):1905–1910.doi.org/10.5958/0974-360X.2020.00343.1.

30. Pargi PM. Purohit BM. Hadiyel LN. Roy T. Mukhopadhyay D. Ghosh S. et al. Metoprolol Induced Oral Lichen Planus in An Adult Female Patient – A Case Report. Research Journal of Pharmacy and Technology. 2020;13(9):4274–4276.doi.org/10.5958/0974-360X.2020.00754.4.

31. Jose J. Ashwini PB. Nayak P. Charyulu RN. Oral Dispersible Films, Novel Technology for the Delivery of Drugs. Research Journal of Pharmacy and Technology. 2019;12(1):425–428.doi.org/10.5958/0974-360X.2019.00077.5.

32. Hajishengallis G. Lamont RJ. Beyond the Red Complex and into More Complexity: The Polymicrobial Synergy and Dysbiosis (PSD) Model of Periodontal Disease Etiology. 2012;27(6):409–419.doi.org/10.1111/j.2041-1014.2012.00663.x.

33. Quamilla N. Stres dan Kejadian Periodontitis (Kajian Literatur). 2016;8.

34. Hendrawati H. Agustha HN. Sari R. Topical Application of Snail Mucin Gel Enhances the Number of Osteoblasts in Periodontitis Rat Model. 2019;52(2):61–65.doi.org/10.20473/j.djmkg.v52.i2.p61-65.

35. Fatikhah N. Yubiliana G. Rinawan FR. Electronic Application for Oral Health School Programme Enhances the Quality of the Information in Dental Health Data Records. 2020;53(4):206–211.doi.org/10.20473/j.djmkg.v53.i4.p206-211.

36. Thiele S. Rauner M. Goes P. Recent Advances in Periodontitis, a Prototypic Osteo-Immunological Disease. AME Publishing Company. 2018;3(0):

37. Kinane DF. Stathopoulou PG. Papapanou PN. Periodontal Diseases. 2017;317038.doi.org/10.1038/nrdp.2017.38.

38. Nield-Gehrig, JS. Willmann, DE. Foundations of Periodontics for the Dental Hygienist. Wolters Kluwer, Lippincot. Williams & Wilkins. 2003;

39. Carranza FA. Camargo P. Periodontal Pocket. In : Newman MG, Takei HH, Klokkevold PR, Carranza FA, Editors. Carranza’s Clinical Periodontology. Saunders Elsevier, Philadelphia. 2006;

40. Shetty SS. Quays DR. John J. Yee NS. Appu D. a/p.Tze LM. Chuen TS. et al. Effect of Oil Pulling on Oral Health- A Microbiological Study. Research Journal of Pharmacy and Technology. 2019;12(1):01–04.doi.org/10.5958/0974-360X.2019.00001.5.

41. Meenambiga SS. Rajagopal K. Shevalkar M. Endophytic Fungi, A Novel Source in the Treatment of Oral Infections. Research Journal of Pharmacy and Technology. 2020;13(6):2936–2942.doi.org/10.5958/0974-360X.2020.00520.X.

42. Preethi PR. Jayashri P. Influence of Naturally Occurring Phytochemicals on Oral Health. Research Journal of Pharmacy and Technology. 2019;12(8):3979–3983.doi.org/10.5958/0974-360X.2019.00685.1.

43. Pranati T. Anitha R. Rajeshkumar S. Lakshmi T. Preparation of Silver Nanoparticles Using Nutmeg Oleoresin and Its Antimicrobial Activity against Oral Pathogens. Research Journal of Pharmacy and Technology. 2019;12(6):2799–2803.doi.org/10.5958/0974-360X.2019.00471.2.

44. Lavanya E. Ganapathy D. Sheeba S. Effect of Removable Partial Denture on Periodontal Health of Abutments. Research Journal of Pharmacy and Technology. 2018;11(6):2587–2590.doi.org/10.5958/0974-360X.2018.00478.X.

45. Aide MI. Mental Health. 2008;12–15.

46. Bonneville M. O’Brien RL. Born WK. Gammadelta T Cell Effector Functions: A Blend of Innate Programming and Acquired Plasticity. 2010;10(7):467–478.doi.org/10.1038/nri2781.

47. Valdor R. Macian F. Induction and Stability of the Anergic Phenotype in T Cells. 2013;25(4):313–320.doi.org/10.1016/j.smim.2013.10.010.

48. Dutzan N. Konkel JE. Greenwell-Wild T. Moutsopoulos NM. Characterization of the Human Immune Cell Network at the Gingival Barrier. 2016;9 (5):1163–1172.doi.org/10.1038/mi.2015.136.

49. Zhu J. Paul WE. CD4 T Cells: Fates, Functions, and Faults. 2008;112 (5):1557–156910.1182/blood-2008-05-078154.

50. Campbell L. Millhouse E. Malcolm J. Culshaw S. T Cells, Teeth and Tissue Destruction - What Do T Cells Do in Periodontal Disease? 2016;doi.org/10.1111/omi.12144.

51. Chen ML. Sundrud MS. Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases. 2016;22(5):1157–1167.doi.org/10.1097/MIB.0000000000000714.

52. Jarry CR. Duarte PM. Freitas FF. de Macedo CG. Clemente-Napimoga JT. Saba-Chujfi E. et al. Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT), a Novel Osteoclast Activator, in Chronic Periodontitis. 2013;74(7):861–866.doi.org/10.1016/j.humimm.2013.04.013.

53. Di Benedetto A. Gigante I. Colucci S. Grano M. Periodontal Disease: Linking the Primary Inflammation to Bone Loss. 2013;2013503754.doi.org/10.1155/2013/503754.

54. Park YD. Kim YS. Jung YM. Lee SI. Lee YM. Bang JB. et al. Porphyromonas gingivalis Lipopolysaccharide Regulates Interleukin (IL)-17 and IL-23 Expression via SIRT1 Modulation in Human Periodontal Ligament Cells. 2012;60(1):284–293.doi.org/10.1016/j.cyto.2012.05.021.

55. Koide M. Kobayashi Y. Ninomiya T. Nakamura M. Yasuda H. Arai Y. et al. Osteoprotegerin-Deficient Male Mice as a Model for Severe Alveolar Bone Loss: Comparison with RANKL-Overexpressing Transgenic Male Mice. 2013;154(2):773–782.doi.org/10.1210/en.2012-1928.

56. Kajimoto N. de C. de Paiva Buischi Y. Loomer PM. Bromage TG. Ervolino E. et al. Adjuvant Therapy with 1% Alendronate Gel for Experimental Periodontitis Treatment in Rats. 2020;51.doi.org/10.5051/jpis.2100700035.

57. Metzger CE. Narayanan A. Zawieja DC. Bloomfield SA. Inflammatory Bowel Disease in a Rodent Model Alters Osteocyte Protein Levels Controlling Bone Turnover. 2017;32(4):802–813.doi.org/10.1002/jbmr.3027.

58. Xiao W. Li S. Pacios S. Wang Y. Graves DT. Bone Remodeling Under Pathological Conditions. 2016;1817–27.doi.org/10.1159/000351896.

59. Costa LC. Fonseca MA. da.Pinheiro A. da R. Aguiar TR. da S. Machado AN. et al. Chronic Periodontitis and RANKL/OPG Ratio in Peri-Implant Mucosae Inflammation. 2018;29(1):14–22.doi.org/10.1590/0103-6440201801241.

60. Carcuac O. Berglundh T. Composition of Human Peri-Implantitis and Periodontitis Lesions. 2014;93(11):1083–1088.doi.org/10.1177/0022034514551754.

61. Moutsopoulos NM. Zerbe CS. Wild T. Dutzan N. Brenchley L. DiPasquale G. et al. Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. 2017;376(12):1141–1146.doi.org/10.1056/NEJMoa1612197.

62. Carbone F. Crowe LA. Roth A. Burger F. Lenglet S. Braunersreuther V. et al. Treatment with Anti-RANKL Antibody Reduces Infarct Size and Attenuates Dysfunction Impacting on Neutrophil-Mediated Injury. 2016;9482–94.doi.org/10.1016/j.yjmcc.2016.03.013.

63. Nicu EA. Loos BG. Polymorphonuclear Neutrophils in Periodontitis and Their Possible Modulation as a Therapeutic Approach. 2016;71(1):140–163.doi.org/10.1111/prd.12113.

64. Malcolm J. Awang RA. Oliver-Bell J. Butcher JP. Campbell L. Adrados Planell A. et al. IL-33 Exacerbates Periodontal Disease through Induction of RANKL. 2015;94(7):968–97510.1177/0022034515577815.

65. Steinmetz O. Hoch S. Avniel-Polak S. Gavish K. Eli-Berchoer L. Wilensky A. et al. CX3CR1hi Monocyte/Macrophages Support Bacterial Survival and Experimental Infection–Driven Bone Resorption. 2016;213(9):1505–1515.doi.org/10.1093/infdis/jiv763.

66. Yoshihara-Hirata C. Yamashiro K. Yamamoto T. Aoyagi H. Ideguchi H. Kawamura M. et al. Anti-HMGB1 Neutralizing Antibody Attenuates Periodontal Inflammation and Bone Resorption in a Murine Periodontitis Model. 2018;86(5):e00111-18.doi.org/10.1128/IAI.00111-18.

67. Kobayashi T. Yokoyama T. Ito S. Kobayashi D. Yamagata A. Okada M. et al. Periodontal and Serum Protein Profiles in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitor Adalimumab. 2014;85(11):1480–1488.doi.org/10.1902/jop.2014.140194.

68. Schett G. Neurath MF. Resolution of Chronic Inflammatory Disease: Universal and Tissue-Specific Concepts. 2018;9(1):3261.doi.org/10.1038/s41467-018-05800-6.

69. Lam RS. O’Brien-Simpson NM. Hamilton JA. Lenzo JC. Holden JA. Brammar GC. et al. GM-CSF and UPA Are Required for Porphyromonas Gingivalis-Induced Alveolar Bone Loss in a Mouse Periodontitis Model. 2015;93(8):705–715.doi.org/10.1038/icb.2015.25.

70. Fleetwood AJ. O’Brien-Simpson NM. Veith PD. Lam RS. Achuthan A. Cook AD. et al. Porphyromonas gingivalis-Derived RgpA-Kgp Complex Activates the Macrophage Urokinase Plasminogen Activator System: Implications for Periodontitis. 2015;290 (26):16031–16042.doi.org/10.1074/jbc.M115.645572.

71. Wilensky A. Polak D. Houri-Haddad Y. Shapira L. The Role of RgpA in the Pathogenicity of Porphyromonas gingivalis in the Murine Periodontitis Model. 2013;40(10):924–932.doi.org/10.1111/jcpe.12139.

72. Wong DM. Tam V. Lam R. Walsh KA. Tatarczuch L. Pagel CN. et al. Protease-Activated Receptor 2 Has Pivotal Roles in Cellular Mechanisms Involved in Experimental Periodontitis. 2010;78(2):629–638.doi.org/10.1128/IAI.01019-09.

73. Francis N. Ayodele BA. O’Brien-Simpson NM. Birchmeier W. Pike RN. Pagel CN. et al. Keratinocyte-Specific Ablation of Protease-Activated Receptor 2 Prevents Gingival Inflammation and Bone Loss in a Mouse Model of Periodontal Disease. 2018;20(11):e12891.doi.org/10.1111/cmi.12891.

74. Maekawa T. Abe T. Hajishengallis E. Hosur KB. DeAngelis RA. Ricklin D. et al. Genetic and Intervention Studies Implicating Complement C3 as a Major Target for the Treatment of Periodontitis. 2014;192(12):6020–6027.doi.org/10.4049/jimmunol.1400569.

75. Graves DT. Alshabab A. Albiero ML. Mattos M. Corrêa JD. Chen S. et al. Osteocytes Play an Important Role in Experimental Periodontitis in Healthy and Diabetic Mice through Expression of RANKL. 2018;45(3):285–29210.1111/jcpe.12851.

76. Pacios S. Xiao W. Mattos M. Lim J. Tarapore R. Alsadun S. et al. Graves D. Osteoblast Lineage Cells Play an Essential Role in Periodontal Bone Loss Through Activation of Nuclear Factor-Kappa B. 2015;516694.doi.org/10.1038/srep16694.

77. Yang CY. Jeon HH. Alshabab A. Lee YJ. Chung CH. Graves DT. RANKL Deletion in Periodontal Ligament and Bone Lining Cells Blocks Orthodontic Tooth Movement. 2018;10(1):3.doi.org/10.1038/s41368-017-0004-8.

78. Danks L. Komatsu N. Guerrini MM. Sawa S. Armaka M. Kollias G. et al. RANKL Expressed on Synovial Fibroblasts Is Primarily Responsible for Bone Erosions during Joint Inflammation. 2016;75 (6):1187–1195.doi.org/10.1136/annrheumdis-2014-207137.