Oral bisphosphonate-induced osteonecrosis complications in patients undergoing tooth extraction: a systematic review and literature updates.

OBJECTIVE: Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF) pathway, preventing their differentiation, inhibiting anchorage to the cell membrane, and inducing apoptosis. In patients undergoing oral bisphosphonate therapy, oral surgery involves a high risk of developing drug-related osteonecrosis of the jaws (BRONJ/MRONJ), among the possible complications. MATERIALS AND METHODS: A systematic search was carried out on the PubMed, Scopus and Cochrane Library search engines, using the keywords "oral bisphosphonates AND tooth extraction", "third molar extraction AND oral bisphosphonates". In addition, we manually evaluated the articles included in references from other sources and an analysis of the Gray Literature was performed. A secondary outcome was to evaluate the assessment of pharmacological (antibiotics) use in the BRONJ/MRONJ management. The revision protocol followed the indications of the Cochrane Handbook, and was registered in the INPLASY database, while the drafting of the manuscript was based on PRISMA. RESULTS: The results of the systematic review, after the study identification and selection process, included a total of 7 studies: 4 retrospective studies, 2 prospective studies and 1 case report. The main complication was represented by osteonecrosis of the jaws, which appears to be related to the duration of treatment with bisphosphonates; in addition, data regarding the anatomical location of post-extraction sites, the sex and age of patients, comorbidities and various systemic risk factors were extrapolated. The most frequent post-extraction complication in patients treated with oral bisphosphonates is osteonecrosis of the jaws, with a significant prevalence in the posterior region of the mandible. In some cases, delayed healing of the surgical wound was also found; moreover, the duration of exposure to oral bisphosphonates influences the onset of complications. CONCLUSIONS: Ongoing studies continue to unravel the role of the oral environment response in alveolar bone homeostasis and how it might contribute to the induction of BRONJ/MRONJ. Approaching the problem from this perspective could provide new directions for the prevention of BRONJ/MRONJ and expand our understanding of the unique oral microenvironment.

Oral administration of nucleotides in calves: Effects on oxidative status, immune response, and intestinal mucosa development.

The present work aimed to investigate the effects of nucleotide oral administration on oxidative stress biomarkers, immune responses, gut morphology, serum biochemical parameters, and growth performance in calves from birth to 25 d of life. A total of 40 male Holstein Friesian calves were randomly divided in 2 groups. All the calves were born and reared on the same commercial dairy farm. They were fed the same colostrum, milk replacer, and calf starter. Five grams/head of an additive were orally administered with a syringe directly in the mouth to calves of the nucleotide group (NG). The additive contained 74.12 g/100 g of nucleic acids from hydrolyzed yeast, and 75.38% was free nucleotide sodium salt. The other group represented the negative control (CG). At 25 d of life all of the calves were slaughtered. Calves supplemented with nucleotides had a higher final live weight and improved average daily gain, which was associated with better efficiency of nutrient use. Oral nucleotide administration did not affect IgG absorption efficiency; however, NG calves showed greater duodenum villi length and higher crypt depth compared with CG. Oral nucleotide administration increased the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and the antioxidant capacity [ferric reducing antioxidant power and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) scavenging activity] both in plasma and in liver. An enhanced ability of cells to counter reactive oxygen species- and reactive nitrogen species-mediated damage was also observed in peripheral blood mononuclear cells from NG. The findings highlight the effectiveness of oral nucleotide administration, and potentially dietary supplementation of nucleotides, in boosting oxidative and immune status in newborn calves.

Accuracy of Edentulous Computer-Aided Implant Surgery as Compared to Virtual Planning: A Retrospective Multicenter Study.

PURPOSE: To evaluate the accuracy of computer-aided dental implant positions obtained with mucosal-supported templates as compared to Three-Dimensional (3D) planning. MATERIALS AND METHODS: One-hundred implants were inserted into 14 edentulous patients using the All-on-4/6 protocol after surgical virtual planning with RealGUIDE, 3DIEMME, and Geomagic software. After 6 months, three-dimensional neck (V) and apex (S) spatial coordinates of implants and angle inclination displacements as compared to virtual plans were evaluated. RESULTS: The S maxilla coordinates revealed a significant discrepancy between clinical and virtual implant positions (p-value = 0.091). The V coordinates showed no significant differences (p-value = 0.71). The S (p-value = 0.017) and V (p-value = 0.038) mandible coordinates showed significant discrepancies between the clinical and virtual positions of the screws. Implant evaluation showed a 1-mm of the horizontal deviation in the V point and a 1.6-mm deviation in the S point. A mean 5° angular global deviation was detected. The multivariate permutation test of the S (p-value = 0.02) confirmed the difference. Greater errors in the mandible were detected as compared to the maxilla, and a higher S discrepancy was found in the posterior jaw compared to the anterior section of both the mandible and maxilla. CONCLUSIONS: Computer-aided surgery with mucosal-supported templates is a predictable procedure for implant placement. Data showed a discrepancy between the actual dental implant position as compared to the virtual plan, but this was not statistically significant. However, the horizontal and angle deviations detected indicated that flap surgery should be used to prevent implant positioning errors due to poor sensitivity and accuracy in cases of severe jaw atrophy.

A pilot study of human mesenchymal stem cells from visceral and sub-cutaneous fat tissue and their differentiation to osteogenic phenotype.

OBJECTIVE: To evaluate the different behavior of two different human adult adipocytes derived stem cells (hASCs) during proliferation and osteogenic differentiation. PATIENTS AND METHODS: Human adult adipocytes stem cells (hAT-SCs) from visceral (hAV-SCs) and subcutaneous (hAS-SCs) sites were obtained after surgery procedures of seven patients. All samples were fully investigated and the different proliferation rates were evaluated. All MSCs clusters were cultured with an osteogenic and adipogenic differentiation medium. Homogeneous pools of Mesenchymal Stem Cells (MSCs) were confirmed by Flow-Cytometry Analysis (FACS) and Spectrophotometric Assay. The differentiated cells were eventually assessed for the expression of Alkaline Phosphatase (ALP), Alizarin Red (AR) and Oil Red-O (OR-O) detection, and analyzed by the Spectrophotometric Assay. After osteogenic differentiation, the cell clusters were incubated and analyzed with Real Time-Polymerase Chain Reaction (qRT-PCR) and fluorescence microscopy. RESULTS: The FACS analysis performed on hAT-SCs confirmed the homogenous presence of MSCs in all samples. The ALP, AR stain confirmed the osteogenic differentiation capacity of MSCs towards osteoblast-like-cells. The colorimetric cell metabolic activity (MTS) assay showed an increase in the proliferation rate with different values in both sets hAS-SCs vs. hAV-SCs. CONCLUSIONS: These in vitro findings of both hAS-SCs and hAV-SCs suggested an important role of these stem cells for future clinical use in bone regeneration. Indeed, the final outcomes suggested a better performance of cells coming from subcutaneous adipose tissue vs. those from visceral fat tissue.

Narrow single tooth implants for congenitally missing maxillary lateral incisors: a 5-year follow-up.

INTRODUCTION: The maxillary lateral incisor epidemiologically represents the second most common congenitally absent teeth. In literature, different approaches have been proposed, such as canine teeth substitution, traditional prosthetic rehabilitation, adhesive restoration or single-tooth implant. The aim of this investigation was to evaluate the clinical and radiographical effectiveness of narrow single tooth implant treatment for missing maxillary lateral incisors. MATERIALS AND METHODS: A total of 11 subjects, in seven cases bilaterally, were treated in the Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" of Chieti-Pescara, with a radiographical follow-up at 5 years from the loading. RESULTS: At the follow up, no bone defects or pathological gingival probing were present around the peri-implant tissues. No mechanical complications, such as loss of the crown fixation screws or fracture, were reported. CONCLUSIONS: Narrow implants represent a predictable optional treatment for maxillary lateral incisor restoration, with a high-level aesthetic and functional outcome of the rehabilitation.

In vitro interface changes of two vs three narrow-diameter dental implants for screw-retained bar under fatigue loading test.

The mechanical failure of a dental implant is clinically related to a prosthetic overload dissipated on the fixture/abutment complex. The aim of this investigation was to evaluate the fracture strength of two vs three narrow-diameter dental implant configurations for screw-retained bars. Different configurations of screw-retained bars on two narrow-diameter dental implants (Group I) and screw-retained bars on three narrow-diameter dental implants (Group II) were tested under a static fracture loading. A total of 20 specimens, 10 for each group were evaluated. The fracture loading point was significatively higher in Group I (p<0.05). The experimental groups reported high levels of fracture strength under loading that encourages the clinical application of screw-retained bars supported by multiple narrow-diameter implants.

Stimulated mast cells release inflammatory cytokines: potential suppression and therapeutical aspects.

Mast cells (MCs) are derived from bone marrow precursors and are immune cells involved in acute and chronic inflammation. MCs are ubiquitous and play a crucial role in innate and acquired immunity. They are activated through cross-linking of their surface high affinity receptors (FcεRI), leading to immediate secretion of stored inflammatory mediators, and late production and release of pro-inflammatory cytokines/chemokines without degranulation. Therefore, MCs are important in inflammatory responses. Members of the interleukin (IL)-1 cytokine family, such as IL-1 and IL-33, and various antigens markedly increase IL-1 and tumor necrosis factor (TNF) expression and secretion from MCs. One of the latest cytokines is IL-33, an IL-1 family member acting via its ST2/IL-1R4, which has been shown to regulate MCs. IL-1 and IL-33 are cytokines found to be implicated in many inflammatory disorders including rheumatoid arthritis, atherosclerosis and psoriasis. In general, IL-1 family member cytokines play a pro-inflammatory role and increase the pathological state. IL-37 is a member of the IL-1 family with anti-inflammatory activity through inhibition of pro-inflammatory cytokines. IL-37 particularly suppresses IL-1-mediated innate inflammatory response, but also acts on the acquired immune response. IL-37 is activated by pro-inflammatory agents and cytokines, playing a protective role against inflammation. This cytokine is a natural regulator of immunity and is a therapeutic promise against inflammatory diseases. Since IL-1 is produced by and activates MCs to release IL-33 and TNF, here we hypothesize that MCs can be inhibited by IL-37 and therefore reduce their pro-inflammatory activity. However, the maturation, transport and secretion of IL-37 remain to be clarified.

A novel technique to prevent sinus membrane collapse during maxillary sinus floor augmentation without bone graft: technical note.

Different surgical techniques have been developed to reconstruct the posterior maxilla without bone graft. A barrier membrane usually placed internal to the sinus, without stabilizer or bone window, pushed inside the sinus cavity as the ''roof'' of the sinus cavity to preserve the space and help bone regeneration has been used with success. In the present technical report, the heterologous cortical lamina is used for the mechanical support of sinus membranes. The membrane is placed through two lines of 2-3 mm, mesial and distal, created at the top of the antrostomy. The half heterologous membrane is positioned on these lines and pushed to the nose wall of the sinus, and the other half is folded to cover the window. In this way the bone lamina is stable. Cone Beam Computed Tomography was used to evaluate the efficacy of bone lamina to preserve the space in sinus lifting which contributes positively to wound healing and is effective in bone formation without biomaterials.

IL-33 mediates allergy through mast cell activation: Potential inhibitory effect of certain cytokines.

Mast cells (MCs) are hematopoietic immune cells commonly found in adjacent to blood vessels in the lamina propria of airway mucosa. They are important in allergic reactions since the cross-linking of their surface high affinity receptor FceRI induces activation of these cells, and provokes the synthesis, degranulation and release of inflammatory mediators including arachidonic acid-derived eicosanoids (de novo synthesized), stored enzyme mediators, and inflammatory TH1 and TH2 cytokines, and chemokines. Interleukin (IL)-33 participates in innate and adaptive immunity and inflammation and, acting on CD34+ cells, causes MC differentiation and maturation. IL-33 is generated by activated immune cells, and activates MCs which degranulate and release pro-inflammatory mediators. IL-33 is very important in mediating allergic inflammation and can be induced by IL-1 beta. It is also called "alarmin" and is an inflammatory cytokine IL-1 family member, expressed from mocytes and MCs, which binds its receptor ST2, provoking its release after cell damage. MC-derived allergic compounds in response to IL-33 is critical to innate type 2 immunity. IL-37 is expressed by immune and non-immune cells after pro-inflammatory stimulus. IL-37, an anti-inflammatory cytokine, binds IL-18Ra and suppresses pro-inflammatory IL-1 beta released by activated immune cells such as macrophages. Here, we hypothesize that pro-inflammatory IL-1 family member cytokines released by activated MCs, mediating inflammatory allergic phenomenon, can be suppressed by IL-37.

Critical role of inflammatory mast cell in fibrosis: Potential therapeutic effect of IL-37.

BACKGROUND: Fibrosis involves the activation of inflammatory cells, leading to a decrease in physiological function of the affected organ or tissue. AIMS: To update and synthesize relevant information concerning fibrosis into a new hypothesis to explain the pathogenesis of fibrosis and propose potential novel therapeutic approaches. MATERIALS AND METHODS: Literature was reviewed and relevant information is discussed in the context of the pathogenesis of fibrosis. RESULTS: A number of cytokines and their mRNA are involved in the circulatory system and in organs of patients with fibrotic tissues. The profibrotic cytokines are generated by several activated immune cells, including fibroblasts and mast cells (MCs), which are important for tissue inflammatory responses to different types of injury. MC-derived TNF, IL-1, and IL-33 contribute crucially to the initiation of a cascade of the host defence mechanism(s), leading to the fibrosis process. Inhibition of TNF and inflammatory cytokines may slow the progression of fibrosis and improve the pathological status of the affected subject. IL-37 is generated by various types of immune cells and is an IL-1 family member protein. IL-37 is not a receptor antagonist; it binds IL-18 receptor alpha (IL-18Rα) and delivers the inhibitory signal by using TIR8. It has been shown that IL-37 can be protective in inflammation and injury, and inhibits both innate and adaptive immunity. DISCUSSION: IL-37 may be useful for suppression of inflammatory diseases induced by inhibiting MyD88-dependent TLR signalling. In addition, IL-37 downregulates NF-κB induced by TLR2 or TLR4 through a mechanism dependent on IL-18Rα. CONCLUSION: This review summarizes current knowledge on the role of MC in inflammation and tissue/organ fibrosis, with a focus on the therapeutic potential of IL-37-targeting cytokines.

New concepts in neuroinflammation: mast cells pro-inflammatory and anti-inflammatory cytokine mediators.

The activation of brain nociceptors and neurons may lead to neurogenic inflammation, an event that involves immune cells including mast cells (MCs). Microglia are similar to macrophages and secrete pro-inflammatory IL-1 family members and TNF. TNF is rapidly released (first 10 minutes from MC granules) and is subsequently secreted along with other pro-inflammatory cytokines with a new synthesis after several hours. MC-derived TNF is a very powerful pro-inflammatory cytokine which mediates sensitization of the meningeal nociceptors. Here, we report the involvement of MCs in neuroinflammation, the role of inflammatory cytokine IL-1 family members, and of TNF, as well as the potential inhibition of IL-37.

Low-grade chronic inflammation mediated by mast cells in fibromyalgia: role of IL-37.

It has been observed that acute stress causes the activation of TH1 cells, while TH2 cells regulate and act on chronic inflammation. Fibromyalgia (FM) is a chronic, idiopathic disorder which affects about twelve million people in the United States. FM is characterized by chronic widespread pain, fatigue, aching, joint stiffness, depression, cognitive dysfunction and non-restorative sleep. The mechanism of induction of muscle pain and inflammation is not yet clear. In FM there is an increase in reactivity of central neurons with increased sensitivity localized mainly in the CNS. Mast cells are involved in FM by releasing proinflammatory cytokines, chemokines, chemical mediators, and PGD2. TNF is a cytokine generated by MCs and its level is higher in FM. The inhibition of pro-inflammatory IL-1 family members and TNF by IL-37 in FM could have a therapeutic effect. Here, we report for the first time the relationship between MCs, inflammatory cytokines and the new anti-inflammatory cytokine IL-37 in FM.

Predictive Prognostic Value of Tissue-Based MicroRNA Expression in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Oral squamous cell carcinoma (OSCC) is a common type of cancer characterized by a low survival rate, mostly due to local recurrence and metastasis. In view of the importance of predicting tumor behavior in the choice of treatment strategies for OSCC, several studies have attempted to investigate the prognostic value of tissue biomarkers, including microRNA (miRNA). The purpose of this study was to perform a systematic review and meta-analysis to evaluate the relationship between miRNA expression and survival of OSCC patients. Studies were identified by searching on MEDLINE/PubMed, SCOPUS, Web of Science, and Google Scholar. Quality assessment of studies was performed with the Newcastle-Ottawa Scale. Data were collected from cohort studies comparing disease-free survival and overall survival in patients with high miRNA expression compared to those with low expression. A total of 15 studies featuring 1,200 OSCC samples, predominantly from Asia, met the inclusion criteria and were included in the meta-analysis. Poor prognosis correlated with upregulation of 9 miRNAs (miR-21, miR-455-5p, miiR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181) and downregulation of 7 miRNAs (miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b). The pooled hazard ratio values (95% confidence interval) related to different miRNA expression for overall survival and disease-free survival were 2.65 (2.07-3.39) and 1.95 (1.28-2.98), respectively. The results of this meta-analysis revealed that the expression levels of specific miRNAs can robustly predict prognosis of OSCC patients.

Different signals induce mast cell inflammatory activity: inhibitory effect of Vitamin E.

Vitamin supplementation in disease reduces morbidity and mortality in humans by promoting the activation of different genes which influence several pathways. The purpose of this article is to clarify the role of vitamin E in mast cell inflammation. Vitamin E is a fat soluble antioxidant which protects from low-density lipoprotein (LDL) oxidation. Vitamin E promotes a barrier function and anti-inflammatory responses by binding the regulatory domain of protein kinase Cα (pkcα) (a regulator and antagonist of heart failure) and decreases the activation of NF-қb, a proinflammatory transcription factor, causing the generation of cytokines/chemokines and mast cell activation. Mast cells participate in innate and acquired immunity and inflammation. Several factors, including cytokines and chemokines, regulate the development and migration of activated mast cells. Mast cells generate and release inflammatory compounds in asthma and allergic diseases and have a detrimental effect on the vessel wall, which can be inhibited by vitamin E. Vitamin E inhibits histamine release generated in activated mast cells, increases calcium Ca2+ uptake and prevents the oxidation of unsaturated fatty acids. Vitamin E is relatively non-toxic, however, administered at very high doses may suppress normal hematological response as well as causing other adverse effects. Therefore, vitamin E may be beneficial in the prevention of diseases mediated by mast cells and can have special value in the treatment of asthma and allergic diseases; however, the exact mechanism by which vitamin E acts is still unclear, thus warranting future research.

Etiological periodontal treatment with and without low-level laser therapy on IL-1ß level in gingival crevicular fluid: an in vivo multicentric pilot study.

Cytokine proteins may have important roles during different human physiological and pathological processes. In the oral cavity, the bone loss and periodontal tissue pathology was related to inflammatory process activation. The aim of the present study was to assess the effects of etiological periodontal therapy with and without the use of Low Level Laser Therapy (LLLT) on clinical periodontal parameters and interleukin (IL)-1ß level in gingival crevicular fluid (GCF) from chronic periodontitis (CP) patients. Thirty non-smoker CP patients were selected from the Foggia University Dental Clinic and other 2 private dental clinics. All patients were divided into two homogeneous randomized groups: 15 patients were treated with only scaling and root planing (group 1) and 15 patients with scaling and root planing etiological treatment and LLLT (group 2). In all sites, at baseline before treatment, the periodontal pocket depth (PPD) and bleeding on probing (BOP) were measured. In the PPD sites, the GCF samples were collected from 30 deep (≥5 mm) and shallow (≤3 mm) sites and IL-1ß were evaluated at baseline, after 10 days and 1 month. In all the samples at baseline, the IL-1ß concentration in GCF and BOP rate were significantly higher at deep PPD sites than at the shallow ones. After 10 days in all samples no PPD improvement was observed in the BOP rate but the IL-1 ß level was statistically significantly improved (p<0.005) in group 2 compared to group 1. At 10 days and 1 month, in all deep PPD sites, PPD and BOP improvements were observed. At same time, IL-1ß levels were lower and statistically significantly (p<0.005) improved in group 2 compared to group 1. The results confirmed that the periodontal etiology treatment of deep PPD sites with or with-out associated LLLT promotes periodontal health. Etiological treatment associated with LLLT, improves BOP and inflammation in periodontal disease. Moreover, the IL-1ß concentration changes in GCF suggest these cytokines as a predictable marker of gingival inflammation in chronic periodontitis patients.

IL-1 haplotype analysis in periodontal disease.

Numerous studies have established statistical associations of the IL-1 gene cluster polymorphisms with various inflammatory diseases. Deriving from that, the present study was intended to determine whether single-nucleotide polymorphisms (SNPs) in these gene are also associated with periodontal disease in a Linkage disequilibrium analysis. This investigation also created two haplotype blocks, both consisting of two different SNPs. Recent theoretical analyses indicate that research with an interpretation of periodontal disease as a complex, oligogenic disorder, with IL-1 genetic variation contributes an important but not exclusive influence on disease risk. Further studies are needed to confirm these results and to understand the mechanisms behind the observed association between IL-1 SNPs and periodontal disease.

Mast cell in innate immunity mediated by proinflammatory and antiinflammatory IL-1 family members.

Innate immunity consists of physical and chemical barriers which provide the early defense against infections. Innate immunity orchestrates the defense of the host with cellular and biochemical proteins. Mast cells (MCs) are involved in innate and adaptive immunity and are the first line of defense which generates multiple inflammatory cytokines/chemokines in response to numerous antigens. MC-activated antigen receptor Fc-RI provokes a number of important biochemical pathways with secretion of numerous vasoactive, chemoattractant and inflammatory compounds which participate in allergic and inflammatory diseases. MCs can also be activated by Th1 cytokines and generate pre-formed and de novo inflammatory mediators, including TNF. IL-37 is an anti-inflammatory cytokine which binds IL-18R-alpha chain and reduces the production of inflammatory IL-1 family members. IL-37 down-regulates innate immunity by inhibiting macrophage response and its accumulation and reduces the cytokines that mediate inflammatory diseases. Here, we discuss the relationship between MCs, innate immunity, and pro-inflammatory and anti-inflammatory cytokines.

A New Total Digital Smile Planning Technique (3D-DSP) to Fabricate CAD-CAM Mockups for Esthetic Crowns and Veneers.

Purpose. Recently, the request of patients is changed in terms of not only esthetic but also previsualization therapy planning. The aim of this study is to evaluate a new 3D-CAD-CAM digital planning technique that uses a total digital smile process. Materials and Methods. Study participants included 28 adult dental patients, aged 19 to 53 years, with no oral, periodontal, or systemic diseases. For each patient, 3 intra- and extraoral pictures and intraoral digital impressions were taken. The digital images improved from the 2D Digital Smile System software and the scanner stereolithographic (STL) file was matched into the 3D-Digital Smile System to obtain a virtual previsualization of teeth and smile design. Then, the mockups were milled using a CAM system. Minimally invasive preparation was carried out on the enamel surface with the mockups as position guides. Results. The patients found both the digital smile design previsualization (64.3%) and the milling mockup test (85.7%) very effective. Conclusions. The new total 3D digital planning technique is a predictably and minimally invasive technique, allows easy diagnosis, and improves the communication with the patient and helps to reduce the working time and the errors usually associated with the classical prosthodontic manual step.

Vascular endothelial growth factor and nitric oxide synthase expression in human tooth germ development.

Vascular Endothelia Growth Factor (VEGF) and Nitric Oxide Synthase (NOS) expression, were evaluated in human tooth germs at two different stages of embryogenesis, to clarify the role of angiogenesis during tooth tissue differentiation and growth. Seventy-two third molar germ specimens were selected during oral surgery. Thirty-six were in the early stage and 36 in the later stage of tooth development. The samples were evaluated with Semi-quantitative Reverse Transcription-Polymerase chain Reaction analyses (RT-PcR), Western blot analysis (WB) and immunohistochemical analysis. Western blot and immunohistochemical analysis showed a VEGF and NOS 1-2-3 positive reaction in all samples analysed. VEGF high positive decrease reaction was observed in stellate reticulum cells, ameloblast and odontoblast clusters in early stage compared to later stage of tooth germ development. Comparable VEGF expression was observed in endothelial cells of early and advanced stage growth. NOS1 and NOS3 expressions showed a high increased value in stellate reticulum cells, and ameloblast and odontoblast clusters in advanced stage compared to early stage of development. The absence or only moderate positive reaction of NOS2 was detected in all the different tissues. Positive NOS2 expression showed in advanced stage of tissue development compared to early stage. The action of VEGF and NOS molecules are important mediators of angiogenesis during dental tissue development. VEGF high positive expression in stellate reticulum cells in the early stage of tooth development compared to the later stage and the other cell types, suggests a critical role of the stellate reticulum during dental embryo-morphogenesis.

Orthodontic forces modulate insulin-like growth factor binding protein-5 changes in gingival crevicular fluid.

Orthodontic tooth movement results from the response of the periodontal tissue to orthodontic force, which leads to modeling and remodeling of the surrounding alveolar bone. The response is considered to occur through the activation of specific signaling pathways, many of which are known, all acting to ultimately result in tooth movement. Much is known about the actions of these two cells, and the signaling pathways that affect them, both in bone and orthodontic literature, however, to date, little work has been carried out to examine the effect of the insulin-like growth factor binding proteins (IGFBP) in orthodontics. Therefore, we investigated the presence of IGFBP-5 in the gingival crevicular fluid (GCF) of 6 healthy subjects, and assessed the effects of orthodontic treatment on the levels and molecular state of this protein.