Massimo Costalonga DMD, PhD


Pathogenesis of Periodontitis
Current Thinking

is 2 to 3

Tooth chrown

Massimo Costalonga D.M.D., Ph.D.
Department of Developmental
and Surgical Sciences

Alveolar bone


Infection of the gingiva
Gingival recession
Loss of bone
Tooth mobility
Halitosis (bad breath)

Disease that is not
reversible but ONLY

Periodontal diseases:
• Infectious diseases that results in
chronic inflammation of the soft tissue
surrounding the gingival pockets.
• Destroys the bone and soft tissue
connection between the gingiva and
the root of the tooth (Kornman 1987,
Suzuki 1988)


PhD Chronic periodontitis is associated with a variety of bacterial species DENT5301 Cultivable microorganisms ¾ Bacteriological and immunological studies implicated a number of subgingival organisms associated with chronic adult periodontitis. Green. (Red. et al. Purple and Yellow complexes) (Socransky et al.Massimo Costalonga DMD. 1997 Do you think we can culture all bacteria in periodontal pocket ? Most microorganisms are uncultivable Talk with the person next to you about this NOW Kumar PS et al. 2005 2 . Orange. gramnegative bacteria may compose 75% of the bacteria (Robertson 1985) Modified from Socransky S. 1997) ¾ In advanced adult periodontitis.

2005 Initial Gingivitis Acute inflammation Epithelium PMNs Chemokines Cytokines Korman KS et al. Periodontology 2000 Vol.Massimo Costalonga DMD. Periodontology 2000 Vol. 14 1997. 33-53 How are these microbes sensed or detected by our body? Talk with the person next to you about this NOW Korman KS et al. 14 1997. 33-53 3 . PhD DENT5301 16S RNA sequences separated health and disease Bacterial biofilm Bacterial challenge Innate immunity first Kumar PS et al.

Massimo Costalonga DMD. PhD DENT5301 PRRs Neutropenia = Low PMN counts INNATE cellular response • Monocytes/macrophages • Neutrophils • Natural Killer (NK) Recognition of Pathogen Associated Molecular Patterns (PAMPs) by Pattern Recognition Receptors (PRRs) Downloaded from: Carranza’s Clinical Periodontology (on 4 August 2006 06:34 PM) IL-8 Lipid mediators of inflammation •Increase •Increase vascular vascular permeability permeability •Increase •Increase smooth smooth muscle muscle contraction contraction •Increase •Increase smooth smooth muscle muscle contraction contraction 4 .

PhD DENT5301 Linoleic acid in plasma membrane Phospholipase C Inhibited by STEROIDS Inhibited by NSAID Lipid mediators of • Prostaglandins • Thromboxans • Leukotrienes T-cell and B-cell mediated immunity in periodontal tissues INNATE IMMUNITY PENETRATION LYMPHOCYTE MICROBIAL DC and AND ACTIVATION ADHERENCE Macrophages INFECTION Resolution Inflammation • Lipoxins • Resolvins • Protectins Toll-like receptors (TLRs) ANTIBODY Activated MACROPHAGES 5 .Massimo Costalonga DMD.

Extracellular microorganisms are phagocytosed 2. Destroyed and reduced in peptides 3.Massimo Costalonga DMD. Presented to T cells via MHC class II molecules T helper 1 (Th1) T helper cells (CD4+) T helper 2 (Th2) Interferon-γ (IFNγ) Interleukin-4 (IL-4) Cell-mediated immunity Antibody immunity 6 . PhD DENT5301 Exogenous pathway In the lymph nodes T cells recognize such microbial peptides via the T cell receptor and…… 1.

Th1 vs. Th2 in periodontal disease T helper 1 cytokine IFNγ protects from disease T helper 2 cytokine IL-4 does not protect from disease Cells in Periodontal Tissues • Gingivitis lesion: mainly T helper 1 lymphocytes (Th1) • Periodontitis lesion: mainly activated B cells and plasmacells – Activation of B cells is dependent on T helper 2 lymphocytes (Th2) WHY ??? 7 . 1997). IFNγ and TNF-α) promotes susceptibility to periodontitis (Chapple C. neutrophils and cell-mediated immunity (Th1) limit attachment loss (Page et al. • Lack of cell-mediated immunity (IL-12. PhD DENT5301 Immune response and periodontitis in humans • In individuals resistant to periodontitis. 1998). • Antigen Presenting Cells from patients susceptible to periodontitis may have a bias towards a Th2 response and thereby promoting an ineffective humoral immunity in periodontitis (Fokkema S.Massimo Costalonga DMD. 2002).

IL-8. IgA IFNγ IFNγ sRANKL CD4 CD4 mRANKL sRANKL UNPROTECTIVE Osteoclast Precursor Precursor RANK ++ M-CSF M-CSF Osteoclast Osteoclast Precursor Precursor TRAP++ Osteoclast Bone Bone Bone Destruction 8 . IL-12. PhD DENT5301 Destruction phase • Cytokine production most important IL1β but also TNF-α.Massimo Costalonga DMD. IL-6. IL-15 and chemokines MCP-1 and RANTES Induction of bone loss • Osteoclast progenitors express the receptor activator of NF-κB (RANK) • Cytokine-induced alteration of the connective tissue metabolism • Activated T cells express the receptor activator of NF-κB Ligand (RANKL) • Imbalance between collagenases and matrix metalloproteinases (MMPs) activity and collagen synthesis • RANK / RANKL interaction + M-CSF generates Tartarate-Resistant Acid Phosphatase positive (TRAP+) osteoclasts => BONE RESORPTION • IL-1β and IL-6 induce fibroblast and osteoclast activation Tissue Macrophage Working Model T helper 1 T helper 2 IL-4 and IL-10 B220 B cell T cell CD4 IgG2a IgG2a mRANKL B220 B220 B cell T cell RANK IgG1.

PhD Induced Protection and Therapeutic Future • Osteoprotegrin (OPG) is a decoy receptor that binds membrane bound and soluble RANKL on activated T and B cells • Potassium channel blocker (Kaliotoxin) reduce the expression of RANKL on T cells DENT5301 Potassium channel blocker (kaliotoxin) B220 B cell T helper 2 T cell CD4 mRANKL Osteoprotegrin (OPG) sRANKL RANK Osteoclast Precursor Precursor ++ M-CSF M-CSF TRAP++ Osteoclast Bone Destruction Conclusion • Th1 type response IFNγ-mediated protects from disease progression. • Interference with RANK .Massimo Costalonga DMD.RANKL interaction of affects the degree of bone loss • Cytokines and lipid mediators may mediate systemic effects that increase the risk of preterm birth and/or low birth weight 9 . • Th2 type response IL-4 and IL10-mediated are inefficient at controlling microbial biofilm.