Effect of Periodontal Pathogens on Total Bone Volume Fraction: A Phenotypic Study

Abstract

Studies have shown that periodontal pathogens can enter the bloodstream, causing a series of reactions that can lead to a variety of systemic diseases. Epidemiological investigations also found a tight correlation between periodontitis (PD) and osteoporosis. This study aimed to further explore the effect of periodontal pathogens on bone volume fraction like bone tissue and mass, and explain the relationship between PD and osteoporosis. Sprague Dawley rats (female, 16 weeks old) were divided into the wild-type (WT) control group (n=9) and PD group (n=9). After eight weeks, periodontal tissues and ligatures, the fourth lumbar vertebra, the femur, the tibia, and blood were extracted and analyzed by micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, tartrate-resistant acid phosphatase (TRAP) staining, polymerase chain reaction (PCR), and enzyme-linked immunoassay (ELISA), respectively. We found that the bone mass of the lumbar vertebra, femur, and tibia was decreased in the PD group. The number of osteoclasts was higher in bone tissue in the PD group than in the WT group (P<0.05). The levels of inflammatory mediators and type I collagen C-terminal peptide (CTX-1) were higher in the PD group than in the WT group (P<0.05), although no significant difference in bone glutamic acid protein (BGP) levels was observed (P>0.05). In addition, we detected several periodontal pathogens, such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Fusobacterium nucleatum, in blood samples from rats in the PD group. These findings suggest that periodontal pathogens can enter the blood circulation from periodontal tissue, promote a systemic inflammation response, and subsequently reduce systemic bone density.

Keywords

periodontitis / periodontal pathogens / bone mineral density / inflammation / systemic disease

References

[1] CaoCF. Prevalences of periodontal diseases and dental caries in China: re-analysis of the data from the Third National Epidemiological Survey on Oral Health. Zhonghua Kou Qiang Yi Xue Za Zhi (Chinese), 2013, 48(5): 257-259

[2] RobertsAP, MullanyP. Oral biofilms: a reservoir of transferable, bacterial, antimicrobial resistance. Expert Rev Anti Infect Ther, 2010, 8(12): 1441-1450

[3] DarveauR. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol, 2010, 8(7): 481-490

[4] NazirMA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci (Qassim), 2017, 11(2): 72-80

[5] JosephML. Adverse outcomes of osteoporotic fractures in the general population. J Bone Miner Res, 2003, 18(6): 1139-1141

[6] XueJ. Epidemiological survey of osteoporosis. New Med Sci Osteop (Chinese), 2007, 38(1): 7-8

[7] MaZJ, WangJ. Epidemiology of Osteoporosis. Internat J Osteol (Chinese), 2007, 28(5): 315-316

[8] DoddDZ, RoweDJ. The relationship between postmenopausal osteoporosis and periodontal disease. J Dent Hyg, 2013, 87(6): 336-344

[9] JuluriR, PrashanthE, GopalakrishnanD, et al.. Association of Postmenopausal Osteoporosis and Periodontal Disease: A Double-Blind Case-Control Study. J Int Oral Health, 2015, 7(9): 119-123

[10] HabashnehR, AlchalabiH, KhaderYS, et al.. Association between periodontal disease and osteoporosis in postmenopausal women in Jordan. J Periodontol, 2010, 81(11): 1613-1621

[11] XieM, TangQ, NieJ, et al.. BMAL1-Downregulation Aggravates Porphyromonas Gingivalis-Induced Atherosclerosis by Encouraging Oxidative Stress. Circ Res, 2020, 126(6): e15-e29

[12] Joseph MeltonL3rd. Adverse outcomes of osteoporotic fractures in the general population. J Bone Miner Res, 2003, 18(6): 1139-1141

[13] LiuY, WangL, KikuiriT, et al.. Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-gamma and TNF-alpha. Nat Med, 2011, 17(12): 1594-1601

[14] LinTH, LungCC, SuHP, et al.. Association between periodontal disease and osteoporosis by gender: a nationwide population-based cohort study. Medicine, 2015, 94(7): e553

[15] KobayashiM, MatsumotoC, HirataM, et al.. The correlation between postmenopausal osteoporosis and inflammatory periodontitis regarding bone loss in experimental models. Exp Anim, 2012, 61(2): 183-187

[16] MariaB, MartinaE, JoshE, et al.. Periodontal Disease and Osteoporosis-Shared Risk Factors and Potentiation of Pathogenic Mechanisms. Current Oral Health Reports, 2018, 5(7): 1-7

[17] SousaLH, LinharesEV, AlexandreJT, et al.. Effects of Atorvastatin on Periodontitis of Rats Subjected to Glucocorticoid-Induced Osteoporosis. J Periodontol, 2016, 87(10): 1206-1216

[18] ChoiJK, KimYT, KweonHI, et al.. Effect of periodontitis on the development of osteoporosis: results from a nationwide population-based cohort study (2003–2013). BMC Womens Health, 2017, 17(1): 77

[19] MohammedN, KismaM, TurkiM, et al.. Serum Osteocalcin and Serum Osteopontin Levels in Osteoporotic Postmenopausal Women with and without Vertebral Fractures. J Fac Med Baghdad, 2015, 5757(33): 257-262

[20] CarleneP, Mariani MélissaK, YawenY, et al.. Interleukin (IL)-6 Inhibits IL-27- and IL-30-Mediated Inflammatory Responses in Human Monocytes. Front Immunol, 2018, 9: 256

[21] Verena M, Penninger J. RANK and RANKL of Bones, T Cells, and the Mammary Glands. Osteoimmunology, 2016:121–142

[22] WangL, ShiX, ZhaoR, et al.. Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-kappaB activation, osteoclastogenesis and bone resorption. Bone, 2010, 46(5): 1369-1379

[23] MaedaK, TakahashiN, KobayashiY. Roles of Wnt signals in bone resorption during physiological and pathological states. J Mol Med (Berl), 2013, 91(1): 15-23

[24] TrindadeSC, OlczakT, Gomes-FilhoIS, et al.. Porphyromonas gingivalis HmuY-induced production of interleukin-6 and IL-6 polymorphism in chronic periodontitis. J Periodontol, 2013, 84(5): 650-655

[25] SongJ, JingZ, HuW, et al.. alpha-Linolenic Acid Inhibits Receptor Activator of NF-kappaB Ligand Induced (RANKL-Induced) Osteoclastogenesis and Prevents Inflammatory Bone Loss via Downregulation of Nuclear Factor-KappaB-Inducible Nitric Oxide Synthases (NF-kappaB-iNOS) Signaling Pathways. Med Sci Monit, 2017, 23: 5056-5069

[26] HienzSA, SwetaP, SasoI. Mechanisms of Bone Resorption in Periodontitis. J Immunol Res, 2015, 2015: 54-61

[27] LarryJ, CássioL, ChristinaM, et al.. Oral infection of mice with Fusobacterium nucleatum results in macrophage recruitment to the dental pulp and bone resorption. Biomed J, 2018, 41(3): 184-193

[28] MurakamiS, MealeyBL, MariottiA, et al.. Dental plaque-induced gingival conditions. J Periodontol, 2018, 89(Suppl 1): S17-S27

[29] AmarS, EngelkeM. Periodontal innate immune mechanisms relevant to atherosclerosis. Mol Oral Microbiol, 2015, 30(3): 171-185

[30] NoraS, LoretoA, DenisseB, et al.. Host response mechanisms in periodontal diseases. J Appl Oral Sci, 2015, 23(3): 329-355

[31] GustavVN, Anna-MartE. Inflammation-induced metabolic derangements or adaptation: An immunometabolic perspective. Cytokine Growth Factor Rev, 2018, 43: 47-53

[32] ZiebolzD, PabelSO, LangeK, et al.. Clinical periodontal and microbiologic parameters in patients with rheumatoid arthritis. J Periodontol, 2011, 82(10): 1424-1432

[33] ShiheidoY, MaejimaY, SuzukiJI, et al.. Porphyromonas gingivalis, a periodontal pathogen, enhances myocardial vulnerability, thereby promoting post-infarct cardiac rupture. J Mol Cell Cardiol, 2016, 99: 123-137

[34] SjogrenK, EngdahlC, HenningP, et al.. The gut microbiota regulates bone mass in mice. J Bone Miner Res, 2012, 27(6): 1357-1367