transforming-growth-factor-beta and Dental-Pulp-Diseases

When bioactive molecules such as bone sialoprotein (BSP), bone morphogenetic protein-7 (BMP-7, also termed OP-1) and chondrogenic Inducing Agents (CIA, A+4 and A-4) were implanted in the pulp of the first upper molars, mineralizations were induced. They were either limited to the formation of a reparative dentinal bridge closing the pulpal wound (CIA A+4), or filled the mesial part of the coronal pulp (BSP), or filled totally the pulp located in the root canal (BMP-7 and CIA A-4). Consequently, these molecules may change in the next future the every day practice in dentistry.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Dental Implants; Dental Pulp; Dental Pulp Capping; Dental Pulp Cavity; Dental Pulp Diseases; Dentinogenesis; Drug Carriers; Integrin-Binding Sialoprotein; Molar; Proteins; Rats; Recombinant Fusion Proteins; Sialoglycoproteins; Tissue Engineering; Transforming Growth Factor beta

Molecular biology is providing opportunities to develop new strategies or agents for the treatment of a wide variety of diseases. The availability of large amounts of highly purified proteins produced by recombinant DNA techniques is an obvious example. Recent evidence has implicated proteins belonging to the bone morphogenetic protein (BMP) subgroup of the transforming growth factor beta supergene family in tooth formation and dentinogenesis. It has long been known that bone and dentin contain bone morphogenetic protein activity. Recently, recombinant human BMP-2, -4, and -7 (also known as OP-1), have been shown to induce reparative dentin formation in experimental models of large direct pulp exposures in permanent teeth. The manner in which these agents act appears unique. New reparative dentin replaces the stimulating agents applied directly to the partially amputated pulp. Hence, the new tissue forms contiguous with, largely superficial to, and not at the expense of the remaining vital pulp tissue. This suggests a therapeutic approach permitting the induction of a predetermined and controlled amount of reparative dentin. Additionally, OP-1 has been associated with the formation of reparative dentin after application to a freshly cut but intact layer of dentin. These findings may provide future clinicians with additional options for the treatment of substantially damaged or diseased vital teeth.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Dental Pulp; Dental Pulp Diseases; Dentin; Dentin, Secondary; Dentinogenesis; Growth Substances; Humans; Molecular Biology; Odontogenesis; Proteins; Recombinant Proteins; Transforming Growth Factor beta

Apical periodontitis is an inflammatory disease of the periradicular tissues caused by the host's immune response to infection of the root canal system. MicroRNAs (miRNAs) have been shown to play an important role in the regulation of inflammation and the immune response; however, their role in the pathogenesis of endodontic periapical disease has not been explored. The purpose of this study was to examine the differential expression of miRNAs in diseased periapical tissues as compared with healthy controls.. We first compared miRNA profiles in diseased periapical tissues collected from patients undergoing endodontic surgery with those of healthy pulps by using microarray analyses. The target genes of the differentially expressed miRNAs were identified by using miRWalk and PubMed. Selected miRNAs linked to inflammation and the immune response were then confirmed in a separate cohort of diseased and healthy tissues by using quantitative reverse transcription-polymerase chain reaction. Healthy pulps and periodontal ligaments were used as controls. Data were normalized to the level of SNORD 44, which served as an endogenous control.. Of the 381 miRNAs identified by using microarray, 24 miRNAs were down-regulated in diseased periapical tissues compared with controls (n = 13) (P < .003). The down-regulation of 7 miRNAs was confirmed from 9 selected miRNAs by using quantitative real-time polymerase chain reaction (n = 19) (P < .05). Target genes of these miRNAs include key mediators in the immune and inflammatory response such as interleukin-6, matrix metalloproteinase-9, and transforming growth factor-β.. These findings offer new insight into the pathogenesis of endodontic disease and have the potential to impact the development of new methods for prevention, diagnosis, and treatment of apical periodontitis.

Topics: Adolescent; Adult; Aged; Apicoectomy; Computational Biology; Dental Pulp; Dental Pulp Diseases; Down-Regulation; Female; Granulation Tissue; Humans; Interleukin-6; Male; Matrix Metalloproteinase 9; Microarray Analysis; MicroRNAs; Middle Aged; Periapical Periodontitis; Periodontal Ligament; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta; Young Adult

To examine cytokine expression profiles during periapical lesion development in response to synergetic human pathogens in a gnotobiotic mouse model.. Human strains of Fusobacterium nucleatum and Peptostreptococcus prevotii were inoculated into the root canals of germ-free mice in either mono- or bi-association. Animals were killed 7 and 14 days after infection, and periapical tissues were collected. mRNA expression of the cytokines IFN-γ, TNF-α, Receptor activator of nuclear factor kappa-B ligand (RANKL), IL-10, IL-4 and transforming growth factor β (TGF-β) was assessed using real-time PCR. Levene's test was used to assess the equality of variance of the data, whereas a t-test for independent samples was used to evaluate the significance of the differences between groups (P < 0.05).. The mRNA expression of IFN-γ and TNF-α was up-regulated by F. nucleatum during the acute (day 7) and chronic phase (day 14) of periapical lesion development. However, in bi-infection the expression of IFN-γ and TNF-α were effectively absent at both time-points. RANKL mRNA expression was down-regulated during dual infection at the chronic phase. As IL-4 expression was similar at both time-points, IL-4 does not appear to be involved in the periapical response to these bacterial strains. IL-10 was up-regulated during the chronic phase by mono-infection with either F. nucleatum or P. prevotii. Dual infection increased TGF-β mRNA expression on day 7, which paralleled the decrease in IFN-γ and TNF-α mRNA levels at the same time-point. F. nucleatum increased TGF-β mRNA expression during the chronic phase.. Cytokine profiles depend on the nature of the bacterial challenge. Both TGF-β and IL-10 appeared to be regulating the proinflammatory cytokine responses at both time-points of the periapical immune response.

Topics: Animals; Coinfection; Cytokines; Dental Pulp Diseases; Fusobacterium Infections; Fusobacterium nucleatum; Germ-Free Life; Gram-Positive Bacterial Infections; Humans; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-4; Mice; Peptostreptococcus; Periapical Diseases; RANK Ligand; Real-Time Polymerase Chain Reaction; RNA, Messenger; Time Factors; Transforming Growth Factor beta; Up-Regulation

The present study was undertaken to evaluate the applicability of chitosan monomer (D-glucosamine hydrochloride) as a pulp capping medicament. Both in vitro and in vivo experiments were carried out to study the cell metabolism and wound healing mechanisms following the application of chitomonosaccharide. After 3 days of osteoblast culture, alkaline phosphatase (ALP) activity significantly increased in the chitosan group. Reverse transcription polymerase chain reaction analysis revealed that chitosan induced an increase in the expression of ALP mRNA after 3 days and bone morphogenetic protein-2 mRNA after 7 days of osteoblast incubation. Inflammatory cytokine, interleukin (IL)-8, synthesis in fibroblasts was strongly suppressed in the medium supplemented with chitosan monomer. Histopathological effects were evaluated in rat experiments. After 1 day, inflammatory cell infiltrations were observed to be weak when compared with the application of chitosan polymer. After 3 days, a remarkable proliferation of fibroblasts was seen near the applied chitosan monomer. The inflammatory cell infiltration had almost completely disappeared. After 5 days, the fibroblastic proliferation progressed, and some odontoblastic cells appeared at the periphery of the proliferated fibroblasts. These findings indicate that the present study is the first report that chitosan monomer acts as a biocompatibility stable medicament even at the initial stage of wound healing in comparison with the application of chitosan polymer.

Topics: Alkaline Phosphatase; Animals; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cells, Cultured; Chitosan; Dental Pulp Diseases; Humans; Interleukin-8; Rats; Regeneration; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor beta

Topics: Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Collagen; Dental Pulp Diseases; Humans; Proteins; Root Canal Therapy; Transforming Growth Factor beta