Differential cytokine expressions affect the severity of peri-implant disease.

OBJECTIVE This study assessed gene expression by quantitative polymerase chain reaction of inflammatory- [interleukin (IL)-12, tumor necrosis factor-alpha (TNF-alpha), IL-4, and IL-10] and osteoclastogenesis-related factors [receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG)] in sites exhibiting different severities of peri-implant disease. MATERIAL AND METHODS Peri-implant soft tissue biopsies (n=48) were harvested from healthy implant (HI), mucositis (MC), initial peri-implantitis (IP) and severe peri-implantitis (SP) sites. RESULTS IL-12 and TNF-alpha mRNA levels were higher in SP, followed by IP and MC (P <0.05). IL-4 was higher in HI, followed by MC, SP and IP (P <0.05). IL-10 was the lowest in HI, while no differences were detected among the diseased groups (P>0.05). OPG mRNA levels were higher in HI, followed by IP, SP and MC, whereas RANKL was increased as the peri-implantitis severity increased (P<0.05). The highest OPG/RANKL ratio was observed in HI and the lowest in SP (P<0.01). CONCLUSION These findings suggest that expressions of inflammatory- and osteoclastogenesis-related factors may play an important role in the onset and severity of the peri-implant diseases.

[1]  G. Roodman.  Regulation of Osteoclast Differentiation , 2006, Annals of the New York Academy of Sciences.

[2]  G Shimamoto,et al.  Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density , 1997, Cell.

[3]  M. Mochizuki,et al.  Suppression by IL-10 and IL-4 of cytokine production induced by two-way autologous mixed lymphocyte reaction. , 1996, Cytokine.

[4]  K Yano,et al.  Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Medzhitov.  Recognition of microorganisms and activation of the immune response , 2007, Nature.

[6]  N. Lang,et al.  The microbiota associated with successful or failing osseointegrated titanium implants. , 1987, Oral microbiology and immunology.

[7]  Björn Klinge,et al.  A systematic review of the incidence of biological and technical complications in implant dentistry reported in prospective longitudinal studies of at least 5 years. , 2002, Journal of clinical periodontology.

[8]  F. Annunziato,et al.  Immune mechanisms in the pathogenesis of inflammatory gastrointestinal disorders. , 1996, The Italian journal of gastroenterology.

[9]  Sundeep Khosla,et al.  Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. , 2008, Endocrine reviews.

[10]  E. Durmuş,et al.  Interleukin-1beta, tumor necrosis factor-alpha levels and neutrophil elastase activity in peri-implant crevicular fluid. , 2002, Clinical oral implants research.

[11]  W. Zou,et al.  Tumor necrosis factor‐α mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism † , 2001, Journal of cellular biochemistry.

[12]  G. Garlet,et al.  Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease. , 2003, Journal of periodontal research.

[13]  Kozo Nakamura,et al.  Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL–RANK signaling system , 2005, Immunological reviews.

[14]  D. Chaplin,et al.  1. Overview of the human immune response. , 2006, The Journal of allergy and clinical immunology.

[15]  S. Akira,et al.  MyD88 But Not TRIF Is Essential for Osteoclastogenesis Induced by Lipopolysaccharide, Diacyl Lipopeptide, and IL-1α , 2004, The Journal of experimental medicine.

[16]  N. Lang,et al.  Experimentally induced peri-implant mucositis. A clinical study in humans. , 1994, Clinical oral implants research.

[17]  P. Scheurich,et al.  Tumor necrosis factors in 1998. , 1998, Cytokine & growth factor reviews.

[18]  S. Yamasaki,et al.  Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. , 2000, Biochemical and biophysical research communications.

[19]  E. Machtei,et al.  Comparison of clinical, radiographic and immunological parameters of teeth and different dental implant platforms. , 2006, Clinical oral implants research.

[20]  M. Trevisan,et al.  Reproducibility of Probing Depth Measurements Using a Constant-Force Electronic Probe: Analysis of Inter- and Intraexaminer Variability. , 2003, Journal of periodontology.

[21]  R. Pacifici,et al.  The role of T lymphocytes in bone metabolism , 2005, Immunological reviews.

[22]  T. Matsuguchi,et al.  Gene Expression of Osteoclast Differentiation Factor Is Induced by Lipopolysaccharide in Mouse Osteoblasts Via Toll-Like Receptors1 , 2001, The Journal of Immunology.

[23]  T. Martin,et al.  Activated T lymphocytes support osteoclast formation in vitro. , 1999, Biochemical and biophysical research communications.

[24]  G. Bellone,et al.  Transforming Growth Factor-β and Interleukin 10 in Oral Implant Sites in Humans , 2003 .

[25]  R. Müller,et al.  IL-10, But Not IL-4, Suppresses Infection-Stimulated Bone Resorption In Vivo1 , 2000, The Journal of Immunology.

[26]  I. Holen,et al.  Role of osteoprotegerin (OPG) in cancer. , 2006, Clinical science.

[27]  D. Lacey,et al.  Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells , 1999 .

[28]  J. Penninger,et al.  Receptor Activator of NF-κB Ligand and Osteoprotegerin Regulate Proinflammatory Cytokine Production in Mice1 , 2006, The Journal of Immunology.

[29]  David L. Lacey,et al.  Osteoclast differentiation and activation , 2003, Nature.

[30]  E. Schwarz,et al.  TNFα and pathologic bone resorption , 2005 .

[31]  Gerald Grütz,et al.  New insights into the molecular mechanism of interleukin‐10‐mediated immunosuppression , 2005, Journal of leukocyte biology.

[32]  S. Santavirta,et al.  Immunohistochemical evaluation of inflammatory mediators in failing implants. , 2006, The International journal of periodontics & restorative dentistry.

[33]  L. Shapira,et al.  A localized absence of interleukin-4 triggers periodontal disease activity: a novel hypothesis. , 1992, Medical hypotheses.

[34]  Josef M. Penninger,et al.  Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand , 1999, Nature.

[35]  Nagihan Bostanci,et al.  Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. , 2007, Journal of clinical periodontology.

[36]  B. Troen.  Molecular mechanisms underlying osteoclast formation and activation , 2003, Experimental Gerontology.