transforming-growth-factor-beta and Periodontal-Diseases

Elastic system fibers are composed of two distinct elements, elastin, which is an amorphous component crosslinked in the core, and microfibril, localized in the periphery of elastin. As microfibrillar proteins, fibrillins, microfibril-associated glycoproteins (MAGPs), latent TGF-beta-binding proteins (LTBPs), microfibril-associated proteins (MFAPs), and fibulins are known. Fibrillin-1 is a major microfibrillar protein and characterized by calcium binding EGF-like (cbEGF) domain. Association between fibrillin-1 and TGF-beta is a recent topic of this field and this interaction is known to inactivate and target TGF-beta action. FBN1 encoding fibrillin-1 is a responsible gene for Marfan syndrome type 1 (MIM #154700), characterized by increased height and long limbs, ectopia lentis, and cardiovascular disorders, such as mitral valve prolapse and aortic dilation and regurgitation. Animal models suggest that the abnormal TGF-beta signaling is underlying as the pathogenesis of these conditions. Besides skeletal, ocular and cardiovascular conditions, severe periodontitis is frequently seen in affected patients. To clarify the unknown function of elastic system fibers in the periodontal ligament (PDL), PDL-cells were isolated from a Marfan syndrome type 1 patient who was with the severe periodontitis and had a mutation in one of the cbEGF domain of fibrillin-1. These results suggested that wild-type fibrillin-1 was required for the normal cell alignment and tissue architecture of PDLs. Evidences are now accumulated to suggest that fibrillin-1 is one of the molecule involved in the interaction between cell and extracellular matrix.

Topics: Fibrillin-1; Fibrillins; Humans; Marfan Syndrome; Microfilament Proteins; Periodontal Diseases; Periodontium; Reference Values; Signal Transduction; Transforming Growth Factor beta

Surgical placement of endosseous oral implants is governed by the prosthetic design and by the morphology and quality of the alveolar bone. Nevertheless, often implant placement may be complexed, if at all possible, by alveolar ridge irregularities resulting from periodontal disease, and chronic and acute trauma. In consequence, implant positioning commonly necessitates bone augmentation procedures. One objective of our laboratory is to evaluate the biologic potential of bone morphogenetic proteins (BMP) and other candidate biologics, bone biomaterials, and devices for alveolar ridge augmentation and implant fixation using discriminating large animal models. This focused review illustrates the unique biologic potential, the clinical relevance and perspectives of recombinant human BMP-2 (rhBMP-2) using a variety of carrier technologies to induce local bone formation and implant osseointegration for inlay and onlay indications. Our studies demonstrate a clinically relevant potential of a purpose-designed titanium porous oxide implant surface as stand-alone technology to deliver rhBMP-2 for alveolar augmentation. In perspective, merits and shortcomings of current treatment protocol including bone biomaterials and guided bone regeneration are addressed and explained. We demonstrate that rhBMP-2 has unparalleled potential to augment alveolar bone, and support implant osseointegration and long-term functional loading. Inclusion of rhBMP-2 for alveolar augmentation and osseointegration will not only enhance predictability of existing clinical protocol but also radically change current treatment paradigms.

Topics: Alveolar Ridge Augmentation; Animals; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Substitutes; Dental Implantation, Endosseous; Dental Implants; Dental Prosthesis Design; Disease Models, Animal; Drug Carriers; Guided Tissue Regeneration; Humans; Osseointegration; Osteogenesis; Periodontal Diseases; Recombinant Proteins; Transforming Growth Factor beta

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. Growth factors are critical to the development, maturation, maintenance and repair of craniofacial tissues, as they establish an extracellular environment that is conducive to cell and tissue growth. Tissue-engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. These materials have been constructed into devices that can be used as vehicles for delivery of cells, growth factors and DNA. In this review, different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral- and tooth-supporting structures, namely the periodontium and alveolar bone.

Topics: Animals; Becaplermin; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Drug Delivery Systems; Genetic Therapy; Growth Substances; Humans; Mouth Diseases; Periodontal Diseases; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Tissue Engineering; Transforming Growth Factor beta; Wound Healing

Topics: Alveolar Bone Loss; Animals; Biomarkers; Bone Resorption; Collagen; Collagen Type I; Endothelial Growth Factors; Epidermal Growth Factor; Extracellular Matrix Proteins; Gingival Crevicular Fluid; Gingivitis; Glycosaminoglycans; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Lymphokines; Osteocalcin; Peptides; Periodontal Diseases; Periodontal Index; Periodontitis; Platelet-Derived Growth Factor; Protein Isoforms; Proteoglycans; Transforming Growth Factor alpha; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Bone morphogenetic proteins (BMPs) include a large number of proteins belonging to the TGF-beta superfamily which are characterized by their ability to induce bone and cartilage formation. Since the isolation and purification of BMPs by recombinant technology, the effects of single BMPs can now be evaluated in animal models. Subcutanous placement of a single recombinant BMP, such as recombinant human (rh) BMP-2, in a rat ectopic assay shows recruitment of undifferentiated mesenchymal cells, cartilage formation, followed by replacement with bone, formation of its own bone marrow and physiological bone remodelling. The therapeutic use of recombinant BMPs in the treatment of periodontal disease (destruction of the tooth ligaments, surrounding bone and tooth cementum, the latter of which anchors the ligaments to the tooth surface from the adjacent tooth socket) has attracted considerable interest due to their potent ability to stimulate intramembranous bone formation without an endochondral intermediate. Their predictability in stimulating new bone may provide an alternative that has greater osteogenic potential than autogenous bone, other growth factors and bone substitutes. The biological processes and the potential role of growth factors involved in promoting regeneration are complicated by the involvement of different cell types each with their different growth rates and responses to various stimuli. The major cell types involved in periodontal regeneration include osteoblasts, cementoblasts and fibroblasts. Here, the formation of the new mineralized layers on the tooth and bone surfaces by cementoblasts and osteoblasts respectively are a prerequisite before periodontal ligament formation and attachment by fibroblasts can occur. In this regard, BMPs are likely candidates to stimulate periodontal regeneration because of their ability not only to promote osteogenesis but also to stimulate cementogenesis (new cementum formation). However, understanding when to manipulate each of the various cells differentiation pathway with the application of single or multiple doses of BMPs at the appropriate concentration is dependent upon a suitable delivery system that can be modified in order to optimize its effect during periodontal wound healing. Furthermore, treatment of intrabony periodontal defects with BMPs are likely to not only require appropriate temporal release of the agent, but also adaptation of a carrier that is robust enough to maintain its integrity aro

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Drug Carriers; Drug Delivery Systems; Humans; Osteogenesis; Periodontal Diseases; Recombinant Proteins; Transforming Growth Factor beta; Wound Healing

Regenerative procedures using barrier membrane technology are presently well established in periodontology and implantology. Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) are based on the premise that barrier membrane materials will promote selective cell re-population and subsequent reconstitution of the periodontal attachment apparatus as well as bone. However, because the predictability of these techniques can be variable, the application of this technology may frequently be restricted to specific case types. There has been increasing interest in the possibility of pharmacologically enhancing regeneration of periodontal and osseous tissues, thereby ultimately providing a more significant and predictable clinical outcome. Bone Morphogenetic Proteins (BMPs) have been isolated, cloned and evaluated in various pre-clinical and clinical models. The results of recent studies involving regeneration of alveolar bone in conjunction with implant therapy and regeneration of PDL attachment with BMPs have been very encouraging. In particular, rhBMP-2 has been shown to promote a degree of osseous and periodontal repair which is significantly greater than that previously seen with conventional GTR/GBR therapies and/or the use of various osseous grafting materials.

Topics: Alveolar Bone Loss; Alveolar Process; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Dental Implantation, Endosseous; Guided Tissue Regeneration, Periodontal; Humans; Membranes, Artificial; Periodontal Attachment Loss; Periodontal Diseases; Periodontal Ligament; Recombinant Proteins; Tissue Engineering; Transforming Growth Factor beta; Treatment Outcome; Wound Healing

Soluble proteins that serve as mediators of cell function and are produced by various cell types, such as structural and inflammatory cells, are collectively called cytokines. Several lines of evidence have revealed that cytokines play important roles not only in tissue homeostasis but also in the pathogenesis of many infectious diseases. Recent research on biological activities in normal periodontium and the pathogenesis of periodontal diseases has clarified the involvement of various cytokines in the biological activities observed in the sites. Cytokines play crucial roles in the maintenance of tissue homeostasis, a process which requires a delicate balance between anabolic and catabolic activities. In particular, growth factors--such as fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), transforming growth factor-beta (TGF-beta)--are thought to play important roles in modulating the proliferation and/or migration of structural cells in the periodontium and the production of various extracellular matrices by these cells. On the other hand, there is little doubt that excessive and/or continuous production of cytokines in inflamed periodontal tissues is responsible for the progress of periodontitis and periodontal tissue destruction. Particularly, inflammatory cytokines--such as IL-1 alpha, IL-1 beta, IL-6, and IL-8--are present in the diseased periodontal tissues, and their unrestricted production seems to play a role in chronic leukocyte recruitment and tissue destruction. It is possible that monitoring cytokine production or its profile may allow us to diagnose an individual's periodontal disease status and/or susceptibility to the disease. In addition, although the hypothesis is still controversial, it has been suggested that discrete T-cell subsets (Th1 and Th2) with different cytokine profiles play specific roles in the immunopathogenesis of periodontal diseases.

Topics: Cell Division; Cell Movement; Cytokines; Disease Susceptibility; Extracellular Matrix; Fibroblast Growth Factors; Gene Expression Regulation; Homeostasis; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Leukocytes; Periodontal Diseases; Periodontitis; Periodontium; Platelet-Derived Growth Factor; Somatomedins; T-Lymphocyte Subsets; Transforming Growth Factor beta

The regeneration of periodontal attachment apparatus is particularly difficult to achieve, primarily because of the presence of many different kinds of tissue that must be restored to produce a functional unit. Traditional methods aimed at regenerating the periodontium have limited indications, and their results are not predictable. Recently, investigators have begun to understand the cellular processes necessary for repair and regeneration of periodontal tissues. Proteins called growth factors have been identified that coordinate these cellular events. The growth factors that may contribute to periodontal regeneration include platelet-derived growth factor, insulin-like growth factor, transforming growth factor-beta, and bone morphogenetic proteins. In vitro studies have demonstrated the positive effects of these factors on a number of cell types essential for periodontal regeneration. For instance, it has been shown that platelet-derived and insulin-like growth factors promote proliferation of osteoblasts an periodontal ligament cell-derived fibroblasts. Animal models have also been used to verify that growth factors can enhance regeneration in vivo following periodontal disease and as an adjunct to implant placement. In the future, human clinical trials will be required to identify the ideal growth factors, their proper doses, and the most suitable carrier system for them.

Topics: Animals; Bone Morphogenetic Proteins; Fibroblast Growth Factors; Fibroblasts; Growth Substances; Guided Tissue Regeneration, Periodontal; Humans; Osteoblasts; Periodontal Diseases; Periodontal Ligament; Periodontium; Platelet-Derived Growth Factor; Proteins; Regeneration; Somatomedins; Transforming Growth Factor beta

Human bone contains an abundance of polypeptide growth factors. These growth factors stimulate the proliferation and activity of bone cells and can stimulate bone formation. Data from this laboratory and others suggest that bone growth factors may act to couple bone formation to resorption to maintain bone mass during remodeling. Research is underway to study these growth factors in bones and teeth, and their possible roles in both the pathogenesis and the treatments of osteoporosis and dental diseases.

Topics: Animals; Bone and Bones; Bone Remodeling; Dentin; Estrogens; Growth Disorders; Growth Substances; Humans; Odontoblasts; Odontogenesis; Osteoarthritis; Osteogenesis; Osteoporosis; Periodontal Diseases; Somatomedins; Tooth; Transforming Growth Factor beta; Vitamin D Deficiency

The recognition that synthetic devices can provide functional replacements for failed teeth, or for previously edentulous areas, has resulted in increased emphasis being placed on understanding of the interactions between synthetic materials and host tissues in order for the success of these devices to be optimized. A key to achievement of an optimal biological interface between the implant and the surrounding tissue is through an understanding of host response to materials. This article reviews the biological requirements for implant-tissue integration, with specific focus on the role of adhesion molecules and cytokines (growth factors) in this process. Adhesion molecule/cytokine interactions are discussed, and in particular the possible role for osteopontin, an adhesion molecule as well as a cytokine, is considered in wound healing. Finally, the causes of peri-implantitis are discussed, and methods of decontamination are presented. The decontamination methods focus on enhancement of cell adhesion and integration to the altered implant surface.

Topics: Cell Adhesion Molecules; Cytokines; Dental Implants; Fibroblast Growth Factor 2; Humans; Integrins; Osseointegration; Osteopontin; Periodontal Diseases; Platelet-Derived Growth Factor; Prosthesis Failure; Sialoglycoproteins; Somatomedins; Transforming Growth Factor beta; Wound Healing

Inflammation of the periodontium leads to connective tissue degradation and eventual tooth loss. The regulation of matrix metalloproteinases (MMPs) has been studied to determine their role in these processes and also during tissue remodelling. Analysis of gingival crevicular fluid has revealed the presence of collagenase and gelatinase that, in the acute stages of periodontal disease, are derived predominantly from polymorphonuclear leukocytes. These MMPs appear to be intimately associated with tissue destruction since the levels of the active forms of these enzymes obtained from either crevicular fluid or mouthrinse samples correlate with tissue destruction and, therefore, provide a sensitive means of demonstrating disease activity. Transforming growth factor-beta, an important regulator of connective tissue remodelling, has been implicated in the rapid remodelling of periodontal tissues. TGF-beta promotes tissue matrix formation by stimulating both the synthesis of matrix proteins (collagen, fibronectin and SPARC) and proteinase inhibitors (TIMP, PAI-1) and by decreasing the synthesis of MMPs, but not the 72 kDa-gelatinase. Nuclear run-on analyses have shown that TGF-beta reduces collagenase and stromelysin synthesis by suppressing gene transcription without altering mRNA stabilities. In contrast, the transcription of the gelatinase and TIMP genes was increased by TGF-beta, which also increased gelatinase mRNA stability. Remodelling of alveolar bone involves interaction between osteoblasts and osteoclasts. Osteoblasts, under the influence of osteotropic hormones (vit D3, PTH and retinoic acid), produce MMPs which appear to function in the removal of soft tissue that precludes access of osteoclasts to the mineralized tissue surface. Rat osteoblastic cells produce MMPs with activity on native collagen, native collagen 3/4-fragments and gelatin and, in addition, two forms of TIMP activity. The 3/4-collagen endopeptidase, purified to apparent homogeneity, also has significant collagenase and gelatinase activities and an amino terminal sequence almost identical to human 72 kDa-gelatinase. The production of this enzyme was stimulated by TGF-beta, which suppresses bone resorption, and by osteotropic hormones which stimulate bone resorption, supporting a bifunctional role for the gelatinase in connective tissue remodelling. Although there is strong evidence for the involvement of MMPs in the resorption of bone and in the inflammation-mediated destruction of per

Topics: Alveolar Bone Loss; Animals; Bone Remodeling; Collagenases; Connective Tissue; Dogs; Fibroblasts; Gingival Pocket; Glycoproteins; Humans; Matrix Metalloproteinase 8; Metalloendopeptidases; Osteoblasts; Periodontal Diseases; Periodontium; Rats; Saliva; Salivary Proteins and Peptides; Tissue Inhibitor of Metalloproteinases; Transforming Growth Factor beta

Matrix metalloproteinases are produced by both defense and structural cells of the periodontium. They are capable of a wide range of interstitial tissue degradation activities. Complex regulating mechanisms include cytokine regulation of genetic transcription, secretion in latent form, which requires activation once produced, and inhibition by specific inhibitors. It appears that these proteinases and their inhibitors, regulating molecules, and associated genetic material are all potential diagnostic markers of periodontal disease. In addition, they can be measured from gingival crevicular fluid or whole saliva. Generally, high inhibitor levels indicate health, and high levels of metalloproteinase indicate disease. Metalloproteinases can also be inhibited by the tetracycline family of drugs to produce clinical benefits. The diagnostic and therapeutic potential of matrix metalloproteinases and their central role in the pathogenesis of periodontal disease serve to emphasize their importance to periodontologists.

Topics: Doxycycline; Extracellular Matrix; Gene Expression Regulation, Enzymologic; Gingival Crevicular Fluid; Humans; Metalloendopeptidases; Periodontal Diseases; Transforming Growth Factor beta

Antibacterial photodynamic treatment (aPDT) has indispensable significance as a means of treating periodontal disorders because of its extraordinary potential for killing pathogenic bacteria by generating an overpowering amount of reactive oxygen species (ROS). The elevated ROS that may result from the antibacterial treatment procedure, however, could exert oxidative pressure inside periodontal pockets, causing irreparable damage to surrounding tissue, an issue that has severely restricted its medicinal applications. Accordingly, herein, we report the use of black phosphorus nanosheets (BPNSs) that can eliminate the side effects of ROS-based aPDT as well as scavenge ROS to produce an antibacterial effect.. The antibacterial effect of ICG/aPDT was observed by direct microscopic colony counting. A microplate reader and confocal microscope enabled measurements of cell viability and the quantification of ROS fluorescence. BPNS administration regulated the oxidative environment. IL-1β, IL-6, TNF-α, IL-10, TGF-β, and Arg-1 mRNA expression levels were used to assess the inflammatory response after BPNS treatment. In vivo, the efficacy of the combination of BPNSs and ICG/aPDT was evaluated in rats with periodontal disease by histomorphometric and immunohistochemical analyses.. The CFU assay results verified the antibacterial effect of ICG/aPDT treatment, and ROS fluorescence quantification by CLSM indicated the antioxidative ability of the BPNSs. IL-1β, IL-6, TNF-α, IL-10, TGF-β, and Arg-1 mRNA expression levels were significantly decreased after BPNS treatment, confirming the in vitro anti-inflammatory effect of this nanomaterial. The histomorphometric and immunohistochemical analyses showed that the levels of proinflammatory factors decreased, suggesting that the BPNSs had anti-inflammatory effects in vivo.. Treatment with antioxidative BPNSs gives new insights into future anti-inflammatory therapies for periodontal disease and other infection-related inflammatory illnesses and provides an approach to combat the flaws of aPDT.

Topics: Animals; Anti-Bacterial Agents; Interleukin-10; Interleukin-6; Periodontal Diseases; Periodontitis; Photochemotherapy; Photosensitizing Agents; Rats; Reactive Oxygen Species; RNA, Messenger; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

The association between periodontopathogenic microbiota and preterm birth (PTB) has been overly studied. However, the biological mechanisms involved are little known. The objective is to evaluate the effect of periodontopathogenic bacteria burden (PBB), periodontal disease and other infections during pregnancy on preterm birth (PTB), through Structural Equation Modeling.. This was a case-control study nested in a prospective cohort called BRISA, including 330 pregnant women, 110 cases and 220 controls. This study included the following variables: cytokines interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), periodontal disease, PBB, age, socioeconomic status (SES), systemic infections and PTB. The correlations between variables were analyzed using Standardized Coefficient (SC).. Greater PBB interfered positively with the occurrence of periodontal disease (SC: 0.027; p: 0.011), but these were not associated with the cytokines studied, nor with PTB. The lower serum levels of IL-10 (SC - 0.330; p 0.022) and TGF-β (SC - 0.612; p  < 0.001), and the presence of other systemic infections during pregnancy (SC 0.159; 0.049) explained the higher occurrence of PTB.. It is possible that only the more severe periodontal disease and other systemic infections are capable of altering the cascade of cytokines regulating the inflammatory process and have an effect on the occurrence of PTB.

Topics: Adult; Age Factors; Case-Control Studies; Cohort Studies; Cytokines; Female; Humans; Infant, Newborn; Interleukin-10; Microbiota; Periodontal Diseases; Pregnancy; Premature Birth; Prospective Studies; Socioeconomic Factors; Transforming Growth Factor beta

Pregnancy is a special period marked with complicated changes in various immune responses. Although pregnant women are prone to developing gingival inflammation, its immunological mechanism remains to be clarified. In a modified ligature-induced periodontal disease murine model, pregnant mice developed more severe alveolar bone loss. Using this model, we investigated the Treg responses during exacerbated periodontal disease in pregnant mice. We tested Treg-associated molecules in gingival tissues by quantitative real-time PCR and found decreased gingival expression of Foxp3, TGFβ, CTLA-4, and CD28 in pregnant mice after periodontal disease induction. We further confirmed that lower number of Treg cells were present in the cervical lymph nodes of pregnant periodontitis mice. Treg cells from the cervical lymph nodes of ligated pregnant mice and non-pregnant mice were tested for their suppressive function in vitro. We manifested that Treg suppressive function was also down-regulated in the pregnant mice. Additionally, we demonstrated that more inflammatory Th17 cells were present in the cervical lymph nodes of ligated pregnant mice. Therefore, impaired Treg development and function, together with upregulated Th17 response, may contribute to the exacerbated periodontal disease during pregnancy.

Topics: Animals; Disease Models, Animal; Disease Progression; Down-Regulation; Female; Forkhead Transcription Factors; Gingivitis; Humans; Mice; Periodontal Diseases; Pregnancy; Pregnancy Complications; T-Lymphocytes, Regulatory; Th17 Cells; Transforming Growth Factor beta

Kindlin-1 is an integrin tail binding protein that controls integrin activation. Mutations in the FERMT-1 gene, which encodes for Kindlin-1, lead to Kindler syndrome in man, which is characterized by skin blistering, premature skin aging and skin cancer of unknown etiology. Here we show that loss of Kindlin-1 in mouse keratinocytes recapitulates Kindler syndrome and also produces enlarged and hyperactive stem cell compartments, which lead to hyperthickened epidermis, ectopic hair follicle development and increased skin tumor susceptibility. Mechanistically, Kindlin-1 controls keratinocyte adhesion through β1-class integrins and proliferation and differentiation of cutaneous epithelial stem cells by promoting α(v)β(6) integrin-mediated transforming growth factor-β (TGF-β) activation and inhibiting Wnt-β-catenin signaling through integrin-independent regulation of Wnt ligand expression. Our findings assign Kindlin-1 the previously unknown and essential task of controlling cutaneous epithelial stem cell homeostasis by balancing TGF-β-mediated growth-inhibitory signals and Wnt-β-catenin-mediated growth-promoting signals.

Topics: Animals; Antigens, Neoplasm; beta Catenin; Blister; Carrier Proteins; Cell Adhesion; Cell Proliferation; Disease Models, Animal; Epidermolysis Bullosa; Hair Follicle; Integrin beta1; Integrins; Keratinocytes; Mice; Mice, Transgenic; Periodontal Diseases; Photosensitivity Disorders; Signal Transduction; Skin; Skin Neoplasms; Stem Cells; Transforming Growth Factor beta; Wnt Proteins; Wnt Signaling Pathway

Kindler syndrome (KS) in humans is a severe skin blistering disease associated with inflammation and increased risk of epidermal squamous cell carcinoma (SCC). This disease is known to be caused by loss-of-function mutations in Kindlin-1, a focal adhesion β-integrin binding protein. Thus far, it has been unclear what specific signaling events occur in KS keratinocytes to promote tumorigenesis, especially since loss of β-integrins and focal adhesion complexes has been previously shown to prevent or delay tumor formation. In the April issue of Nature Medicine, Rognoni and colleagues generate a transgenic mouse lacking Kindlin-1 in the epidermis to model the key features of KS, and show that Kindlin-1 regulates Wnt and TGFβ signaling independent of β-integrins. These β1-integrin-independent functions of Kindlin-1 may contribute to the increased SCC risk in KS patients.

Topics: Animals; Blister; Carrier Proteins; Cell Proliferation; Epidermolysis Bullosa; Keratinocytes; Periodontal Diseases; Photosensitivity Disorders; Skin; Stem Cells; Transforming Growth Factor beta; Wnt Proteins

Transforming Growth Factor-beta1 (TGF-beta1) plays a key role in connective tissue remodeling and inflammation. Under pathological conditions, like periodontal disease, fibroblasts may display an altered response to this growth factor. To investigate this question, we have studied whether TGF-beta1 may differentially regulate the expression of urokinase at the protein level in primary cultures of fibroblasts derived from healthy gingiva, granulation tissue from gingival wounds, and chronic periodontal disease. We observed that TGF-beta1 may repress urokinase expression in healthy gingival fibroblasts and promote its production in granulation-tissue fibroblasts. A significant correlation was found between expression of the myofibroblast marker alpha-smooth-muscle actin and stimulation of urokinase production by TGF-beta1. Immunostaining of gingival wounds showed that myofibroblasts were involved in urokinase production. TGF-beta1-stimulated urokinase expression was blocked after inhibition of the c-jun-NH2 terminal kinase signaling pathway. We propose that stimulation of urokinase production by TGF-beta1 is involved in the responses of activated fibroblasts to tissue injury.

Topics: Actins; Adaptor Proteins, Signal Transducing; Adult; Case-Control Studies; Cells, Cultured; Female; Fibroblasts; Gingiva; Granulation Tissue; Humans; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Periodontal Diseases; Transforming Growth Factor beta; Transforming Growth Factor beta1; Urokinase-Type Plasminogen Activator; Wound Healing

Genetic polymorphisms in the TGF-beta1 gene were shown to interfere with the transcriptional activity of the TGF-beta1 gene, and this influences the production, secretion or activity of the TGF-beta1 growth factor. Transforming growth factor-beta1 (TGF-beta1) gene polymorphism is associated with risk of inflammatory diseases.. The aim of this study was to evaluate TGF-beta1 gene polymorphisms in a Turkish population with different periodontal diseases and to investigate the association between TGF-beta1 genotype and clinical periodontal parameters.. A total of 134 subjects were included in this study. Genomic DNA was isolated from 51 patients with chronic periodontitis (CP), 43 with generalized aggressive periodontitis (G-AgP) and 40 healthy controls. Three TGF-beta1 gene polymorphisms were identified by PCR-RFLP and MS-PCR at positions +915G/C, Thr263Ile and 713/8delC. Probing pocket depth (PPD), clinical attachment loss (CAL), plaque accumulation (plaque %) and bleeding of probing were obtained. Chi-square, Mann-Whitney U test and logistic regression analysis were used.. There was a slightly significant difference in +915C positive genotype distributions between CP and control groups (OR: 2.46, CI: 1.010-6.005, p = 0.047). No significant differences were present between G-AgP and controls in +915C positive genotype. Thr263Ile and -713/8delC genotype distributions were not different between study groups. There were significant differences in PPD and CAL scores between +915C positive and negative CP patients.. These findings suggest that the TGF-beta1 (+915C) polymorphic allele might be associated with chronic periodontitis in the Turkish population.

Topics: Adult; Alleles; Chronic Disease; Female; Gene Frequency; Humans; Male; Middle Aged; Periodontal Diseases; Periodontitis; Polymorphism, Genetic; Regression Analysis; Transforming Growth Factor beta; Turkey

We have investigated whether a purified immunomodulatory water soluble beta-1,3/1,6-glucan isolated from the cell wall of Bakers yeast, Saccharomyces cerevisiae, would influence the progression of ligature-induced periodontal disease, and to modulate accompanying cytokine and hypothalamic-pituitary-adrenal (HPA) axis responses to a lipopolysaccharide (LPS) challenge.. beta-1,3/1,6-glucan (10 mg/kg/day) was given in the drinking water to Wistar rats during the entire experiment, starting 14 days before disease induction, while control rats were given tap water only. Periodontal disease was assessed when the ligatures had been in place for 35 days.. Orally administered soluble beta-1,3/1,6-glucan significantly reduced periodontal bone loss as measured on digital X-rays (p=0,026). Glucan-treated rats also showed a significantly enhanced plasma level of the HPA axis-driven hormone corticosterone (p=0.047), and of the cytokine transforming growth factor-1beta (p=0.032), as well as a tendency to enhanced IL-10 (p=0.106), induced by intra-peritoneally administered LPS.. Soluble beta-1,3/1,6-glucan administered by the oral route diminishes ligature-induced periodontal bone loss in this model. This effect may be attributable to the well documented ability of beta-1,3/1,6-glucan to stimulate macrophage phagocytosis and to skew the T helper (Th)1/Th2 balance towards Th1 and T regulatory responses. The HPA axis may play a significant role in beta-1,3/1,6-glucan induced immune modulation.

Topics: Alveolar Bone Loss; Animals; beta-Glucans; Corticosterone; Glucans; Hypothalamo-Hypophyseal System; Interleukin-10; Ligation; Lipopolysaccharides; Male; Periodontal Diseases; Pituitary-Adrenal System; Rats; Rats, Wistar; Saccharomyces cerevisiae; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

The responsiveness of the sympathetic nervous system (SNS) and the hypothalamic--pituitary--adrenal (HPA) axis plays a major role in immune regulation and for the outcome of infections and inflammatory disorders. This study was designed to investigate whether chemical SNS denervation with the noradrenaline-selective neurotoxic drug 6-hydroxydopamine (6-OHDA), which destroys peripheral noradrenaline terminals, would influence immune responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation, and the progression of ligature-induced periodontal disease in Fischer 344 rats.. 6-OHDA (40--60 microg/kg) or vehicle was injected intraperitoneally (i.p.) on days 1, 3 and 5, 10 days before application of the ligatures, and thereafter weekly in doses of 80 microg/kg. Periodontal disease was assessed when the ligatures had been in place for 49 days. At 24 and 2 h before decapitation, all rats received LPS (150 microg/kg i.p.) to induce a robust immune and HPA axis response.. The 6-OHDA-treated rats showed significantly reduced bone loss as measured by digital X-rays (p< 0.01), and enhanced levels of the cytokines transforming growth factor-beta (p=0.05) and interleukin-6 (p=0.05), as well as the HPA axis derived hormone corticosterone (p=0.01), induced by LPS stimulation.. 6-OHDA-induced chemical sympathectomy inhibits ligature-induced periodontal disease in this model. This effect may be attributable to the well-documented ability of the SNS to regulate immune system function primarily via the adrenergic neurotransmitter noradrenaline released at sympathetic nerve terminals. The enhanced HPA axis activation may be a compensatory response that reduces the T helper (Th)2 to Th1 skewing effect of treatment with 6-OHDA.

Topics: Alveolar Bone Loss; Animals; Corticosterone; Hypothalamo-Hypophyseal System; Injections, Intraperitoneal; Interleukin-10; Interleukin-6; Lipopolysaccharides; Male; Oxidopamine; Periodontal Diseases; Pituitary-Adrenal System; Rats; Rats, Inbred F344; Statistics, Nonparametric; Stress, Psychological; Sympathectomy, Chemical; Sympatholytics; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

CXCL12 is a CXC chemokine that is related to lymphocyte infiltration and angiogenesis in inflammatory sites such as arthritis. However, the expression and roles of CXCL12 in periodontal disease are uncertain. The aim of this study was to assess the expression of CXCL12 and its receptor, CXCR4, in periodontal tissue and to investigate the properties of CXCL12 and CXCR4 expression by human gingival fibroblasts (HGF). RT-PCR analysis revealed that CXCL12 and CXCR4 mRNA were expressed in both normal gingival tissues and periodontal diseased tissues. Immunohistochemistry disclosed that CXCL12 was expressed and CXCR4 positive cells were found in both normal and periodontal diseased gingival tissues. Our in vitro experiments elucidated that HGF constitutively produced CXCL12, and the levels were enhanced by stimulation with tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein 3(alpha) (MIP-3(alpha)). On the other hand, heat killed Porphyromonas gingivalis (P. gingivalis) and P. gingivalis LPS reduced the CXCL12 production by HGF. Flow cytometry analysis clarified that CXCR4 was highly expressed on HGF, and CXCR4 expression was abrogated by TNF-alpha, IFN-gamma and P. gingivalis LPS. Moreover, CXCL12 induced vascular endothelial growth factor (VEGF) production by HGF. Our results demonstrated that CXCL12 might be related to CXCR4+ cells infiltration and angiogenesis both in normal periodontal tissues and periodontal diseased tissue. P. gingivalis, a known periodontal pathogen, inhibits the production of CXCL12 and the expression of CXCR4 by HGF. This fact means that P. gingivalis may inhibit CXCR4+ cells infiltration and neovascularization in periodontal tissue and escape from the immune response.

Topics: Cells, Cultured; Chemokine CCL20; Chemokine CCL5; Chemokine CXCL12; Chemokines, CC; Chemokines, CXC; Fibroblasts; Flow Cytometry; Gingiva; Humans; Immunohistochemistry; Interferon-gamma; Lipopolysaccharides; Macrophage Inflammatory Proteins; Periodontal Diseases; Porphyromonas gingivalis; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Matrix metalloproteinases (MMPs). produced by both infiltrating and resident cells of the periodontium, play a role in physiologic and pathologic events. It is recognized that an imbalance between activated MMPs and their endogenous inhibitors leads to pathologic breakdown of the extracellular matrix during periodontitis. To date, little is known about the regulation of MMP synthesis and secretion in human periodontal ligament fibroblasts (PDLFs). The purpose of this study was to examine the effects of cytokines, pharmacological agents (protein synthesis inhibitor and protein kinase C inhibitors) and predominant periodontal pathogens (Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis) on MMP production in human PDLFs using gelatin zymography. The gelatin zymograms revealed that the main gelatinase secreted by human PDLFs migrated at 72 kDa and represents MMP-2. Minor gelatinolytic bands were also observed at 92 kDa regions that correspond to MMP-9. We found that A. actinomycetemcomitans, P. gingivalis and IL-1alpha can elevate MMP-2 secretion in human PDLFs. These results indicate that periodontal pathogens and inflammatory cytokines play an important role in tissue destruction and disintegration of extracellular matrix in periodontal diseases. Thus, activation of MMPs may be one of the distinct host degradative pathways in the pathogenesis of periodontitis. In addition, H7, staurosporine, cycloheximide and TGF-beta could suppress MMP-2 production. Agents that target protein synthesis or the protein kinase C pathway in human PDLFs inhibit MMP-2 production, and such inhibition may contribute to the pathogenesis of periodontal inflammation. Taken together, these findings suggest a possible new therapeutic approach, involving the use of drugs that modify host-response mechanisms to suppress or inhibit MMP-mediated tissue destruction.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Aggregatibacter actinomycetemcomitans; Cells, Cultured; Cycloheximide; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors; Fibroblasts; Gene Expression Regulation, Enzymologic; Humans; Interleukin-1; Matrix Metalloproteinase 2; Periodontal Diseases; Periodontal Ligament; Porphyromonas gingivalis; Protein Kinase C; Protein Synthesis Inhibitors; Staurosporine; Tissue Inhibitor of Metalloproteinase-2; Transforming Growth Factor beta

Alterations of the host response caused by short-term exposure to high levels of smoke during the act of smoking (acute smoke exposure) as well as long-term exposure to lower levels of tobacco substances in the bloodstream of smokers (chronic smoke exposure) may play a role in the pathogenesis of periodontal diseases in smokers. In this study, we examined the secretion of three cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta] from mononuclear blood cells from current smokers and non-smokers exposed to in vitro tobacco smoke (which may be comparable to in vivo acute smoke exposure) and mononuclear blood cells from current smokers not exposed to further in vitro smoke (which may be comparable to chronic smoke exposure). Peripheral blood mononuclear cells were isolated from eight healthy current smokers and eight healthy non-smokers, plated in culture wells, exposed in vitro for 1-5 min to cigarette smoke in a smoke box system or not exposed (baseline controls), and then incubated without further smoke exposure for another 24 h. Supernatants from each well were then collected and assayed for the concentrations of the three cytokines by enzyme-linked immunosorbent assay (ELISA). At baseline, mean IL-1beta levels were higher in smokers than in non-smokers (mean: 10.6 vs. 5.9 pg/ml, anova: P < 0.05). In both smokers and non-smokers, secreted levels of IL-1beta increased from 0 to 5 min of in vitro smoke exposure (mean: 5.9-9.9 pg/ml, t-test: P < 0.05 for non-smokers only) with levels in smokers higher than in non-smokers (P > 0.05). Mean TNF-alpha levels increased from 0 to 2 min of smoke exposure and decreased from 2 to 5 min in smokers and non-smokers, with higher levels in non-smokers than smokers at all time-points (P > 0.05). Mean TGF-beta levels were higher in smokers than in non-smokers at all time-points (mean: 180.5 vs. 132.0 pg/ml, P < 0.05 at 5 min only) with no significant alteration of the pattern of secretion with cigarette smoke exposure. These observed alterations in the secretion of cytokines from mononuclear blood cells in smokers, relative to non-smokers, and with in vitro smoke exposure may play a role in the pathogenesis of periodontal diseases in smokers.

Topics: Adult; Analysis of Variance; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1; Lymphocytes; Male; Matched-Pair Analysis; Middle Aged; Monocytes; Nicotiana; Periodontal Diseases; Smoke; Smoking; Statistics as Topic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Bone morphogenetic proteins (BMPs) have shown considerable promise as a therapeutic agent to enhance periodontal regeneration although the optimal characteristics of a suitable release system are not known.. The aim of this study was to compare the effects of slow and fast degrading gelatin carriers on BMP-2-induced periodontal healing.. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was incorporated into gelatin and subsequently differentially cross-linked to produce slow and fast release carrier systems. Release kinetics were confirmed in vitro, by measuring release of 125I-growth hormone from similar gelatin plugs. Effects of BMP were evaluated in surgically created rat periodontal fenestration defects which were processed for histology 10 days post-operatively. The rats were divided into 4 groups and the control defects were treated with either slow or fast degrading gelatin (CONs or CONf respectively), whilst test groups were treated with 1.25 microg rhBMP-2 in the slow or fast degrading gelatin (BMPs or BMPf respectively).. BMPf greatly increased bone formation compared with the control (CONf) (1.67 +/- 0.65 versus 0.34 +/- 0.11 x 10(-4) m2), but no significant differences were observed with BMPs and CONs. In contrast, new cementum formation was significantly greater in the BMPs group compared with all other groups (p<0.05).. Release kinetics of BMP may have important effects on the outcome of BMP-induced periodontal regeneration. New bone formation may be affected by rapid-release kinetics although further investigation is necessary to confirm this. In contrast, new cementum formation is promoted by slow release of BMP.

Topics: Alveolar Bone Loss; Alveolar Process; Analysis of Variance; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Delayed-Action Preparations; Dental Cementum; Drug Carriers; Drug Implants; Gels; Humans; Image Processing, Computer-Assisted; Kinetics; Male; Osteogenesis; Periodontal Diseases; Rats; Rats, Wistar; Recombinant Proteins; Regeneration; Statistics as Topic; Transforming Growth Factor beta; Treatment Outcome; Wound Healing

The unique action of bone morphogenetic proteins (BMPs) on mineralised tissue formation indicates that BMPs are good candidates for use in stimulating periodontal regeneration. Relatively little is known about the mechanisms of actions of BMPs during periodontal regeneration, although recent evidence from our laboratory suggests that the effects of BMPs may be profoundly influenced by various factors including root surface conditioning, delivery systems and masticatory forces.. The aim of this study was to investigate the effect of rhBMP-2 on cell recruitment during periodontal regeneration using a pulse-chase technique where cells are labelled with a thymidine analogue (BrdU) (pulse) and the migration of their progeny is followed (chase) during early wound healing. The relationship between the rhBMP-2 influence on cell recruitment from the periodontal ligament (PDL) and its ability to stimulate cementogenesis was also evaluated.. The buccal aspect of the distal root of the first molar was denuded of its PDL, cementum and superficial dentine through a bony window created in the mandible of 64 Wistar rats under general anaesthesia. Test animals were treated with 10 microL of 500 microg/ml rhBMP-2 in a collagen membrane sponge (n=32) and control defects received 10 microl of saline in a collagen sponge (n=32). All animals received an intraperitoneal single pulse injection of 40 mg/kg BrdU label 2 days postoperatively. Groups of test and control animals (n=8) were killed 2 hours later on day 2 and at 4, 7 and 10 days postoperatively. Mandibles were processed for histological examination.. The results show that rhBMP-2 had a profound effect on proliferation and migration of cells in the adjacent and deeper aspects of the PDL at 7 and 10 days post periodontal wounding (p<0.05). Significantly greater new cementum formation occurred in the test group at 10 days (p=0.03).. This study shows that following periodontal wounding rhBMP-2 stimulates cell recruitment by increasing proliferation and migration of cells from the adjacent unwounded PDL into the wounded area, thus promoting periodontal regeneration by increasing new cementum formation.

Topics: Alveolar Bone Loss; Animals; Antibodies, Monoclonal; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bromodeoxyuridine; Cell Division; Cell Movement; Collagen; Coloring Agents; Dental Cementum; Gelatin Sponge, Absorbable; Indicators and Reagents; Membranes, Artificial; Molar; Osteogenesis; Periodontal Diseases; Periodontal Ligament; Rats; Rats, Wistar; Recombinant Proteins; Regeneration; Statistics as Topic; Transforming Growth Factor beta; Wound Healing

In an attempt to understand better the cells responsible for periodontal regeneration, cells from human gingiva, periodontal ligament and regenerating periodontal defects treated with expanded polytetrafluorethylene membranes were isolated, cultured and characterized. Guided tissue regeneration procedures were carried out on three human volunteers around molar teeth destined for extraction. After a 6-week 'healing phase', fibroblast cell cultures were established from explants of the regenerating soft connective tissue (RTF), as well as from the associated periodontal ligament (PLF) and gingiva (GF). Following stimulation with platelet-derived growth factor-beta (PDGF) and insulin-like growth factor-1 (IGF-1), [3H]thymidine-uptake and dye-binding assays were used to assess the rate of DNA synthesis and cell proliferation, respectively. Northern blotting was used to measure the expression of mRNA for the extracellular matrix proteoglycans decorin, biglycan and versican. The results show that the GF and RTF proliferated more quickly than the PLF. PDGF and IGF-1 were mitogenic for all three cell types. Decorin mRNA expression was stronger in the GF than the RTF and PLF, whereas versican mRNA expression was stronger in the GF and PLF than the RTF. Biglycan mRNA expression was strong in the PLF, moderate in the GF and weak in the RTF. The growth factors did not affect the mRNA expression for biglycan, but they upregulated versican and downregulated decorin mRNA. It can be concluded that RTF exhibits properties characteristic of a reparative phenotype. More specifically, it proliferates faster than PLF, from which it is derived, while exhibiting a unique pattern of proteoglycan mRNA expression. Therefore, this study demonstrates that fibroblasts obtained from the regenerating periodontal defects exhibit characteristics consistent with their ability to facilitate periodontal regeneration.

Topics: Adult; Aged; Analysis of Variance; Becaplermin; Biglycan; Blotting, Northern; Cell Division; Cells, Cultured; Chondroitin Sulfate Proteoglycans; Connective Tissue; Decorin; DNA; Down-Regulation; Extracellular Matrix Proteins; Female; Fibroblasts; Gingiva; Guided Tissue Regeneration, Periodontal; Humans; Insulin-Like Growth Factor I; Lectins, C-Type; Male; Middle Aged; Periodontal Diseases; Periodontal Ligament; Phenotype; Platelet-Derived Growth Factor; Proteoglycans; Proto-Oncogene Proteins c-sis; Regeneration; RNA, Messenger; Statistics as Topic; Transforming Growth Factor beta; Up-Regulation; Versicans; Wound Healing

Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1).. Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone. The animals were euthanized at 4 weeks postsurgery and block-biopsies of the defects were processed for histologic and histometric analysis.. Surgical implantation of rhTGF-beta 1 resulted in minimal, if any, stimulation of alveolar bone or cementum regeneration. Linear bone and cementum regeneration in rhTGF-beta 1-treated defects was 1.2+/-0.6 and 0.01+0.01 mm, respectively. Corresponding values for the controls were 1.0+/-0.6 and 0.01+/-0.03 mm.. The results suggest that, under the conditions (dose, carrier, defect type) evaluated here, treatment of periodontal defects in beagle dogs with rhTGF-beta 1 may be of limited clinical benefit.

Topics: Alveolar Process; Animals; Bone Regeneration; Dental Cementum; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Drug Implants; Humans; Male; Periodontal Diseases; Recombinant Proteins; Transforming Growth Factor beta

This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor-beta1 (rhTGF-beta1) in conjunction with guided tissue regeneration (GTR). Supraalveolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-beta1, in a CaCO3/hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control). 20 microg of rhTGF-beta1 in buffer solution was incorporated into approximately 0.8 ml of carrier for each defect scheduled to receive rhTGF-beta1. Animals were sacrificed at week 4 postsurgery and tissue blocks were harvested and processed for histometric analysis. Clinical healing was generally uneventful. Minor membrane exposures were observed. Defects with membrane exposure displayed an inflammatory infiltrate underneath the membrane. Bone regeneration of trabecular nature, apparent in all animals, was generally limited to the very apical aspect of the defects. Cementum regeneration was limited without obvious differences between experimental conditions. Comparing rhTGF-beta1, to control defects, statistically significant differences were found for area (1.8+/-0.4 and 1.3+/-0.6 mm2, respectively; p<0.05) and density (0.3+/-0.1 and 0.2+/-0.03, respectively; p<0.05) of alveolar bone regeneration. Observed differences are small and represent a clinically insignificant potential for enhanced regeneration in this preclinical model. Within the limitations of study, it may be concluded that rhTGF-beta1 has a restricted potential to enhance alveolar bone regeneration in conjunction with GTR.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Bicuspid; Bone Regeneration; Calcium Carbonate; Dental Cementum; Dogs; Drug Carriers; Furcation Defects; Guided Tissue Regeneration, Periodontal; Humans; Hydroxyethyl Starch Derivatives; Membranes, Artificial; Periodontal Diseases; Polytetrafluoroethylene; Recombinant Proteins; Regeneration; Transforming Growth Factor beta

Resorbable collagen membranes for guided tissue regeneration in periodontal therapy have shown promise but are not osteoinductive. As recombinant human bone morphogenetic protein-2 (rhBMP-2) is known to have an affinity for collagen, the use of this osteoinductive agent incorporated into a collagen vehicle may act as a suitable carrier to promote periodontal regeneration. The aim of this study was to investigate the effects of two different collagen delivery systems for rhBMP-2 in rat periodontal fenestration defects. Using the collagen membrane delivery system, 3 groups of adult Wistar rats which had surgical defects created on the right side of the mandible involving the removal of bone and exposure of the molar roots were treated with either rhBMP-2 in colagen membrane (BMPm) (n = 12 animals), or collagen membrane only (COLm) (n = 12), or were left untreated (UN) (n = 14). Using the collagen gel delivery system, surgical defects were treated with either rhBMP-2 incorporated in a collagen gel carrier (BMPg) (n = 5) or had collagen gel only (COLg) (n = 6). Animals were killed 10 d postoperatively and tissues processed for histology. New bone formation was significantly greater in BMPg compared with both BMPm and controls (p < 0.05). However, new cementum formation was significantly greater in BMPm (721 +/- 166 micron2, mean +/- SE) compared with COLm, COLg and UN (p < 0.02) (190 +/- 44 micron2, 327 +/- 114 micron2 and 172 +/- 33 micron2, respectively) and more than 1.5 times BMPg (451 +/- 158 micron2). In conclusion, both carrier systems for rhBMP-2 significantly increased new bone formation compared with controls during the early stages of periodontal wound healing. However, the more slowly dissolving collagen membrane carrier system for rhBMP-2 produced significantly greater new cementum compared with the collagen gel carrier, suggesting that a more prolonged exposure of rhBMP-2 is required to increased cementogenesis.

Topics: Alveolar Bone Loss; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Collagen; Dental Cementum; Drug Carriers; Drug Delivery Systems; Gels; Guided Tissue Regeneration, Periodontal; Humans; Male; Membranes, Artificial; Osteogenesis; Periodontal Diseases; Periodontium; Rats; Rats, Wistar; Recombinant Proteins; Regeneration; Solubility; Time Factors; Transforming Growth Factor beta; Wound Healing

Topics: Animals; Arthritis; Periodontal Diseases; Rats; Transforming Growth Factor beta