Several growth factors (or cytokines) have been recently investigated for their use as potential therapeutics for periodontal tissue regeneration. The objective of this study was to evaluate periodontal tissue regeneration, including new bone and cementum formation, following topical application of recombinant basic fibroblast growth factor (bFGF, FGF-2) to furcation class II defects. Twelve furcation class II bone defects were surgically created in six beagle dogs, then recombinant bFGF (30 micro g/site) + gelatinous carrier was topically applied to the bony defects. Six weeks after application, periodontal regeneration was analyzed. In all sites where bFGF was applied, periodontal ligament formation with new cementum deposits and new bone formation was observed histomorphometrically, in amounts greater than in the control sites. Basic FGF-applied sites exhibited significant regeneration as represented by the new bone formation rate (NBR) (83.6 +/- 14.3%), new trabecular bone formation rate (NTBR) (44.1 +/- 9.5%), and new cementum formation rate (NCR) (97.0 +/- 7.5%). In contrast, in the carrier-only sites, the NBR, NTBR, and NCR were 35.4 +/- 8.9%, 16.6 +/- 6.2%, and 37.2 +/- 15.1%, respectively. Moreover, no instances of epithelial down growth, ankylosis, or root resorption were observed in the bFGF-applied sites examined. The present results indicate that topical application of bFGF can enhance considerable periodontal regeneration in artificially created furcation class II bone defects of beagle dogs.

TLR2 participates, at least partly, in the signaling pathway to induce chemokine production in gingival epithelium as a reaction against Pg component(s), probably other than lipopolysaccharide and fimbriae.

In this study we examined the influence of adenosine on the cellular functions of human gingival fibroblasts (HGF), such as the production of inflammatory cytokines and extracellular matrices (ECM), and the expression and function of adhesion molecules. Concerning the expression of adenosine receptors, RT-PCR analysis revealed that HGF expressed adenosine receptor A1, A2a and A2b, but not A3 mRNA. Ligation of adenosine receptors by adenosine or its related analogue, 2-chloroadenosine (2-CADO), N(6)-cyclopentyladenosine (CPA) or CGS21680 synergistically increased IL-1beta-induced IL-6 and IL-8 production. In terms of ECM expression, adenosine and the adenosine receptor agonists, 2-CADO and CPA, enhanced constitutive and IL-1beta-induced expression of hyaluronate synthase mRNA, but not the mRNA levels of other ECM, such as collagen type I, III and fibronectin. Moreover, the adherence of IL-1beta-stimulated HGF to activated lymphocytes was also inhibited by adenosine, which is in part explained by the fact that adenosine down-regulated the IL-1beta-induced expression of ICAM-1 on HGF. These results provide new evidence for the possible involvement of adenosine in the regulation of inflammatory responses in periodontal tissues.

Chronic adult periodontitis is usually characterized by inflammatory cell accumulation in the extravascular periodontal connective tissue. In order to reveal how the lymphocyte migration and retention in periodontal lesions is regulated, we have focused on the molecular basis for the adhesive interactions between lymphocytes and human gingival fibroblasts (HGF). In this study, we investigated the involvement of cell adhesion molecules in adhesive interactions between lymphocytes and HGF. We found that activated lymphocytes bound strongly to HGF and VLA integrins, extracellular matrix receptors, play crucial roles in the binding. Interestingly, we first revealed that CD44 molecules (hyaluronate receptor) on lymphocytes also participated in lymphocyte-HGF interactions and that hyaluronate anchored on the surface of HGF functioned as the ligand for CD44. In addition, when HGF were stimulated with inflammatory cytokines such as IL-1, TNF alpha and IFN gamma, the binding avidity between lymphocytes and HGF was significantly increased and the adhesion was mainly mediated by LFA-1/ICAM-1 pathway. We then examined the possibility whether lymphocyte-HGF interaction may cause activation of HGF. When HGF directly interacted with lymphocytes for 3 h, IL-1 beta mRNA expression was clearly increased in HGF. These findings suggested that the adhesive interactions between lymphocytes and HGF was mediated at least by VLA integrins, LFA-1/ICAM-1 and CD44/hyaluronate and that the heterotypic cell-cell interactions could mutually cause intracellular signal transduction.

A series of reports has revealed that adenosine has a plethora of biological actions toward a large variety of cells. In this study, we investigated the influence of adenosine receptor activation on iNOS mRNA expression in human gingival epithelial cells (HGEC) and SV-40-transformed HGEC. HGEC expressed adenosine receptor subtypes A1, A2a, and A2b, but not A3 mRNA. Ligation of adenosine receptors by a receptor agonist, 2-chloroadenosine (2CADO), enhanced iNOS mRNA expression by both HGEC and transformed HGEC. In addition, the adenosine receptor agonist enhanced the production of NO(2)(-)/NO(3)(-), NO-derived stable end-products. An enhanced expression of iNOS mRNA and NO(2)(-)/NO(3)(-) was also observed when SV40-transformed HGEC were stimulated with CPA or CGS21680, A1- or A2a-selective adenosine receptor agonists, respectively. These results provide new evidence for the possible involvement of adenosine in the regulation of inflammatory responses by HGEC in periodontal tissues.