Immunohistochemical evaluation of inflammatory mediators in failing implants.

It was hypothesized that peri-implant tissue around loosening dental implants may contain cytokines with a potential to regulate osteoclasts. Peri-implant and/or gingival samples from loosened implants, chronic periodontitis (CP), and normal controls (n = 10 samples in each group) were analyzed using immunohistochemical staining to observe tumor necrosis factor alpha (TNF-alpha), interleukin 1-alpha (IL-1alpha), IL-6, platelet-derived growth factor A (PDGF-A), and transforming growth factor alpha (TGF-alpha). These cytokines were found in foreign-body giant cells, macrophages, fibroblasts, and epithelial cells. TNF-alpha, IL-1alpha, and IL-6 were increased (P < .05; unpaired t test) in peri-implantitis and CP, whereas PDGF-A and TGF-alpha were not. In conclusion, cytokines with a potential to activate osteoclasts were found in both peri-implantitis and CP, but the cytokine profiles differed in that IL-1alpha was the most prevalent cytokine in the former and TNF-alpha was the most common in the latter. These cytokines may contribute to peri-implant bone loss/loosening by stimulating formation and activity of osteoclasts and might be an amenable target for local therapies with cytokine modulators.

Direct evidence of collagenolysis in chronic periodontitis.

BACKGROUND: There is no previous evidence that collagenases in chronic periodontitis excessively cleave collagen fibrils. OBJECTIVES: In this study the eventual presence of neoepitopes produced in such a cleavage were looked for. METHODS: A polyclonal antibody, which recognizes collagenase-cleaved collagen type I 3/4 carboxy-terminal neoepitope (COL1-3/4C), was used in avidin-biotin-peroxidase complex staining. RESULTS: In addition, moderate staining was seen in connective tissue bordering to the sulcular and junctional epithelium, surrounding some of the fibroblasts and in some areas infiltrated by inflammatory mononuclear cells. COL1-3/4C staining in chronic periodontitis was more extensive (6.3 +/- 1.2%, n = 10) and intense than that observed in controls (1.6 +/- 0.7%, n = 10, Unpaired Student's t-test, p < 0.01). CONCLUSIONS: It is concluded that collagenases produced by host cells contribute to periodontal tissue destruction and attachment loss.

Increased expression of a novel osteoclast-stimulating factor, ADAM8, in interface tissue around loosened hip prostheses.

OBJECTIVE: ADAM8 is a protein of a disintegrin and a metalloproteinase family that can induce osteoclast fusion and activity, perhaps via interactions involving integrin receptors and their cysteine-rich/disintegrin domains. Because loosening of hip replacement implants is characterized by foreign body giant cells and peri-implant osteoclasts, it was speculated that this molecule might be (over)expressed in the synovial membrane-like interface tissues. METHODS: In situ hybridization; immunohistochemical staining with or without tartrate-resistant acid phosphatase (TRAP) staining; image analysis/morphometry; isolation, amplification, and cloning of ADAM8; nucleotide sequencing; quantitative reverse transcriptase-polymerase chain reaction (RT-PCR); and Western blot. RESULTS: In situ hybridization disclosed ADAM8 mRNA in mono- and multinuclear cells in both interface and control synovial samples. Quantitative RT-PCR revealed high ADAM8 mRNA copy numbers in interface tissue (p < 0.01). Accordingly, extensive ADAM8 immunoreactivity was observed in the lining-like layers and sublining areas of interface tissue (p < 0.001). A 65 kDa ADAM8 band in Western blot of tissue extracts confirmed these findings. ADAM8/TRAP double staining showed close spatial relationships of ADAM8 positive precursor cells with other precursors and/or TRAP-positive multinuclear cells. CONCLUSION: ADAM8 is (over)expressed in tissues around aseptically loosened total hip implants, which are characterized by chronic foreign body inflammation and peri-implant bone loss. This is compatible with a role for ADAM8 in the formation of foreign body giant cells and osteoclasts.

Gelatinase B is associated with peri-implant bone loss.

The aim of this study was to clear whether gelatinase B is associated with peri-implant bone loss (PBL). Peri-implant sulcus fluid was collected from 46 implant sites in 12 patients. These sites were also characterized using modified Gingival Index (mGI). Activated and total gelatinase B levels, measured using a modified urokinase assay, showed correlation with PBL (n = 46, Spearman's rank correlation test). Activated and total gelatinase B values were significantly higher in PBL > 3 mm group (n = 6) compared to PBL < 1 mm (n = 29) and 1 < PBL < 3 mm (n = 11) groups (rank sum test). Activated gelatinase B level in mGI > 0.5 group (n = 24) was clearly higher compared to mGI = 0 (n = 13) and < or = 0.5 (n = 9) groups (Rank sum test). We conclude that gelatinase B is associated with PBL. Activation of gelatinase B together with elevated mGI eventually reflect active phases of peri-implantitis and may prove to be diagnostically useful.