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Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the

Oral cavity and oropharynx cancer associated with human papil loma virus infection, particularly in young people who are continuously exposed to this virus, is a serious public health problem worldwide, especially for high-risk strains that are most associated with premalignant lesions and tumors. These neoplasms remain asymptomatic for a long time and, when they occur, they are already at an advanced stage. If diagnosed and treated early, oral cancer induced by human papilloma virus allows for high survival, as it often has a more favorable prognosis than oral cancers not directly related to viral infection. In this study, the presence of different high-risk and low-risk HPV strains was investigated to assess the epidemiological status in a population of healthy individuals. Two types of samples, one from the tonsils and one from the base of the tongue, were collected from 2015 healthy individuals of different sex and age. A total of 1885 DNA samples belonging to 1285 patients were tested for the presence of 11 high-risk HPV types plus 4 low-risk HPV types using real-time PCR. Of the patients’ DNA samples screened for 15 HPV types, only four samples were positive, all of which were taken from male smokers. These results indicate that newly acquired oral oncogenic HPV infections in the healthy population are rare and, in many cases, controversial. Therefore, more studies are needed to ensure fewer variations in outcomes and a greater clarification of HPV infection and its prevalence in the oropharynx of the healthy population, and to guide efforts to prevent the development of this infection which, if undiagnosed, can lead to the onset of malignant tumors in the oral cavity.

Introduction. The administration of several classes of drugs can lead to the onset of gingival overgrowth: anticonvulsants, immunosuppressants, and calcium channel blockers. Among the anticonvulsants, the main drug associated with gingival overgrowth is diphenylhydantoin. Materials and Methods. In this study, we compared the effects of diphenylhydantoin and gabapentin on 57 genes belonging to the &ldquo, Extracellular Matrix and Adhesion Molecule&rdquo, pathway, present in human fibroblasts of healthy volunteers. Results. Both molecules induce the same gene expression profile in fibroblasts as well as a significant upregulation of genes involved in extracellular matrix deposition like COL4A1, ITGA7, and LAMB3. The two treatments also induced a significant downregulation of genes involved in the expression of extracellular matrix metalloproteases like MMP11, MMP15, MMP16, MMP24, and transmembrane receptor ITGB4. Conclusions. Data recorded in our study confirmed the hypothesis of a direct action of these drugs at the periodontium level, inducing an increase in matrix production, a reduction in its degradation, and consequently resulting in gingival hyperplasia.

The epithelial and mesenchymal cells involved in early embryonic facial development are guided by complex regulatory mechanisms. Any factor perturbing the growth, approach and fusion of the frontonasal and maxillary processes could result in orofacial clefts that represent the most common craniofacial malformations in humans. The rarest and, probably for this reason, the least studied form of cleft involves only the secondary palate, which is posterior to the incisive foramen. The etiology of cleft palate only is multifactorial and involves both genetic and environmental risk factors. The intention of this review is to give the reader an overview of the efforts made by researchers to shed light on the underlying causes of this birth defect. Most of the scientific papers suggesting potential environmental and genetic causes of non-syndromic cleft palate are summarized in this review, including genome-wide association and gene–environment interaction studies.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.

Berberine (BBR) is a natural active principle with potential antitumor activity. The compound targets multiple cell signaling pathways, including proliferation, differentiation, and epithelial–mesenchymal transition. The aim of this study was to elucidate the mechanisms behind the anticancer activity of BBR by comparing the effects of purified BBR with those of the extract of Tinospora cordifolia, a medicinal plant that produces this metabolite. The expression levels of a panel of 44 selected genes in human colon adenocarcinoma (HCA-7) cell line were quantified by real-time polymerase chain reaction (PCR). BBR treatment resulted in a time- and dose-dependent down regulation of 33 genes differently involved in cell cycle, differentiation, and epithelial–mesenchymal transition. The trend was confirmed across the two types of treatment, the two time points, and the different absolute dosage of BBR. These findings suggest that the presence of BBR in T. cordifolia extract significantly contributes to its antiproliferative activity.

Background: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. Methods: A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. Results: The rs35996865-G allele was under-transmitted in cases of nsCP [P=.006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. Conclusion: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology.

Orofacial clefts are common congenital defects whose prevalence differs between geographical regions and ethnic groups. The inheritance is complex, involving the contribution of both genetic and environmental factors. The involvement of genes belonging to the folate pathway is still matter of debate, with strong evidences of association and conflicting results. After demonstrating the contribution, for a sample from the Italian population, of common mutations mapping on three genes of the folate pathway, our group tried to unravel their contribution in independent sample studies with different ethnicity. In the present investigation a set of 34 triads with oral cleft from Nassiriya, Iraq, has been genotyped for rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS polymorphisms. Association analysis evidenced a decreased risk of cleft for children carrying the 667G allele at TCN2 gene ( P = 0.02). This evidence further supported the relationship between polymorphisms of folate related genes and oral clefts, and outlined the relevance of studying populations having different ethnicity.

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia. Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background.

The objective of this work was a systemic evaluation of the anodizing treatment in a β-type Ti-15Mo alloy to grow a TiO2 nanostructured layer for osseointegration improvement. The technical viability of the surface modification was assessed based on the resistance to mechanical fatigue, electrochemical corrosion, and biological response. By using an organic solution of NH4 F in ethylene glycol, a well-organized array of 90 nm diameter nanotubes was obtained with a potential of 40 V for 6 h, while undefined nanotubes of 25 nm diameter were formed with a potential of 20 V for 1 h. Nevertheless, the production of the 90 nm diameter nanotubes was followed by micrometer pits that significantly reduced the fatigue performance. The undefined nanotubes of 25 nm diameter, besides the greater cell viability and improved osteoblastic cell differentiation in comparison to the as-polished surface, were not deleterious to the fatigue and corrosion properties. This result strengthens the necessity of an overall evaluation of the anodizing treatment, particularly the fatigue resistance, before suggesting it for the design of implants. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 86-96, 2019.

The objective of this study was to evaluate the effects of lozenges-containing Lactobacillus reuteri as an adjuvant treatment of peri-implant mucositis and to detect the level of L. reuteri colonization in the peri-implant tissues of treated patients. A total of 10 patients were selected. Subjects with at least one implant affected by peri-implant mucositis, with gingival index (GI) of ⩾2 in each quadrant, evaluated at the buccal aspect of all teeth. Patients included in the study were partially edentulous and had implants with mucositis or peri-implantitis. Implants with radiographic bone loss of ⩾5 mm and/or ⩾50% of the implant length were excluded, and only one implant per patient was included. Each patient received L. reuteri–containing lozenges. Microbiological sampling was performed at baseline and on day 28 and analysed by polymerase chain reaction (PCR). Our results indicate that the use of the probiotic did not influence the peri-implant microbiota in a statistically significant way, although there was a reduction in the number of periodontal and peri-implant species. The lack of statistically significant microbiological changes could be explained either by the small sample population or by the short evaluation period. Therefore, the poor colonization of L. reuteri in the peri-implant pockets can be explained by the different anatomical and histological characteristics of the interface of the dental–gingival unit with respect to the periodontal sulcus. The administration of a daily lozenge of L. reuteri for 4 weeks had a limited effect on the microbiological analysis. Probiotics provide an alternative therapeutic approach to consider in the prevention and treatment of peri-implant diseases, but further long-term prospective studies with standardized variables are needed.

Background This review aims to address procedures and indications for the application of the adipose-derived stem cells (ADSCs) for regenerative dentistry. ADSCs have rarely been used in this particular field; conversely, experience from other clinical fields and basic research seems to recommend the suitability of this application. Aims and methods We reviewed 32 out of 193 articles on Medline sorted by the relevance option. The main purpose of this paper is to perform a short review of the application of stem cells in regenerative dentistry, describing a multilineage differentiation as a safe and useful alternative way of harvesting and selection of ADSCs. Results and conclusion The most common derivation of stem cells for regenerative dentistry is from the adipose tissue. There are conditions in which the levy adipose cannot be easily achieved, or where large amount of grafting is not needed. For this purpose, the possibility of selecting stromal stem cells directly from the lax subcutaneous connective tissue, preferably of the head region, would allow a technical simplification.

The indication for using chemical devices as an adjunct of domestic oral hygiene has gained increased attention in last decades. The efficacy of chemical devices for oral biofilm control is proven by evidence from clinical studies. The purpose of this study was to assess the effect of a new oral gel named ADC to reduce oral bacterial loading investigated by means of Polymerase Chain Reaction (PCR). Materials and methods A total of 20 patients with a diagnosis of chronic periodontitis in the age group >25 years, were selected. None of these patients had received any surgical or non-surgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. The study sample was divided into two groups of 10 patients each, homogeneous by age and sex. The study group was given a little bottle containing ADC gel, while the control group was given an identical pack-containing placebo, a gel similar to ADC for consistence, colour, taste and odour. Four sites in separate quadrants were selected in each patient for testing the efficacy of the new medical device. Microbial analysis (MA) was performed at baseline and at day 15. Paired T-Test was used to detect statistical significant reduction of total bacterial loading and specific bacteria. Results Specimens of subgingival plaque from patients were investigated for the presence of six bacterial species and for total bacterial loading by quantitative PCR. There was a statistically significant reduction total bacterial loading detected pre and post treatment (p= 0.029) in the study group. In the control group the reduction of total bacterial loading was not significant (p= 0,279). The ADC gel did not show any side effects and was not observed to cause discomfort or to produce adverse reactions in time. No patient reported pain, burning, tingling sensation or numbness. Conclusion The aim of our study was to test the efficacy of a new chemical formulation with antibacterial properties to use for domestic oral hygiene with a preliminary study. Although the reported data show a statistically significant drop in total bacterial loading after treatment our limited results do not allow us to draw final conclusions about the clinical efficiency of the ADC gel. There is currently a trend in the increased use of antimicrobial agents. The effectiveness of antimicrobial therapies depends on host defence mechanisms and virulence factors. Further research, with relatively larger sample size and longer follow-up period, will be performed to better validate the efficacy of ADC gel as an effective local drug delivery agent in daily oral hygiene.

MicroRNAs have recently been proposed as non-invasive biomarkers in Oral Squamous Cell Carcinoma (OSCC). The aim of this study was to analyze the expression of a panel of miRNAs in epithelial cells collected by oral brushing from OSCCs from regenerative areas after OSCC surgical resection and from their respective normal distant mucosa. Oral brushing specimens were collected from 24 healthy donors, 14 OSCC patients with specimens from tumour and normal distant mucosa, and from 13 patients who had OSCC resection, with samples from regenerative areas after OSCC resection and normal distant mucosa. Expression levels of eight targets (miR-21, miR-375, miR-345, miR-181b, miR-146a, miR-649, miR-518b, and miR-191) were evaluated by real-time Polymerase Chain Reaction (PCR). A highly significant between-group difference was found for miR-21 (F = 6.58, p &lt, 0.001), miR-146a (F = 6.974, p &lt, 0.001), and miR-191 (F = 17.07, p &lt, 0.001). The major difference was observed between samples from healthy donors and from OSCC brushing, whereas no significant differences were observed between areas infiltrated by OSCC and their respective normal distant mucosa. Furthermore, altered expression of miR-146a and miR-191 was also observed in regenerative areas after OSCC resection. Conclusions: Oral brushing could be proposed as a noninvasive method to study microRNA expression in oral mucosa in OSCC patients.

Objective: Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state. Materials and methods: Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P. A total of 632 families from Italy and Asia participated to the study. Results: Evidence of allelic association was found with polymorphisms of SNAI1; in particular, the rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds ratio = 0.69 (95% C.I. 0.54–0.89)]. However, the adjusted significance value corrected for all the performed tests was P = 0.051. Conclusions: The findings emerging by the present study suggest for the first time an involvement of SNAI1 in the nsCL/P onset. Clinical relevance: Interestingly, SNAI1 is known to promote epithelial to mesenchymal transition by repressing E-cadherin expression, but it needs an intact PRC2 to act this function. Alterations of this process could contribute to the complex etiology of nsCL/P.

The objective of this work was a systemic evaluation of the anodizing treatment in a β-type Ti-15Mo alloy to grow a TiO

Gene expression and cell behavior are regulated by several factors, including small non-coding RNAs. MicroRNAs affecting cell growth, differentiation, and apoptosis are thought to play an important role in tumorigenesis. The levels of miR-146 appear to be associated with cancer development and progression, including that of oral squamous cell carcinoma. The aim of this investigation was to ascertain whether the single nucleotide polymorphism, rs2910164, mapping in the MIR146A gene, has a role in oral squamous cell carcinoma progression. A genetic association study was performed with a sample set of 346 oral squamous cell carcinomas collected in Italy. Our data indicate that the rs2910164 polymorphism is not associated with tumor development. However, a slight increase in the frequency of the variant allele was observed in Stage II tumors. Further investigations are needed to verify a possible role of the variant allele or rs2910164 in oral squamous cell carcinoma progression.

Berberine (BBR) is a natural active principle with potential antitumor activity. The compound targets multiple cell signaling pathways, including proliferation, differentiation, and epithelial–mesenchymal transition. The aim of this study was to elucidate the mechanisms behind the anticancer activity of BBR by comparing the effects of purified BBR with those of the extract of Tinospora cordifolia, a medicinal plant that produces this metabolite. The expression levels of a panel of 44 selected genes in human colon adenocarcinoma (HCA-7) cell line were quantified by real-time polymerase chain reaction (PCR). BBR treatment resulted in a time- and dose-dependent down regulation of 33 genes differently involved in cell cycle, differentiation, and epithelial–mesenchymal transition. The trend was confirmed across the two types of treatment, the two time points, and the different absolute dosage of BBR. These findings suggest that the presence of BBR in T. cordifolia extract significantly contributes to its antiproliferative activity.

Surface modifications of commercially pure titanium (Cp-Ti), a material widely used to produce dental implants, can induce specific responses on osteoblastic cells after implantation. This work aims to investigate the influence of chemically modified surfaces of Cp-Ti by acid etching or acid etching plus alkaline treatment on the gene expression of human osteoblastic (Hob) cells. Roughness and contact angle measurements were carried out to evaluate the surface properties of the samples. The surface morphology was investigated with scanning electron microscopy. Chemical composition was analyzed by energy dispersive X-ray spectroscopy (EDS). The expression levels of some bone-related genes (ALPL, COL1A1, COL3A1, SPP1, RUNX2, and SPARC) were analyzed using real time Reverse Transcription-Polymerase Chain Reaction (real time RT-PCR). The results showed that all the chemical modifications studied in this work influenced the surface morphology, wettability, roughness and induced an osteoconductive behavior. The samples that were acid etched and alkaline treated showed a more pronounced effect.

The molecular basis of orofacial development is largely unknown and needs to be unravelled. Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial malformation, with an incidence of about 1/700 live births, although variable according to ethnicity. Being a multifactorial disease, it arises as a result of an interplay between genetic and environmental factors. Several approaches have been developed to identify susceptibility genes. Genes belonging to the folate/homocysteine pathway are attracting increasing interest because folate supplementation before and during early pregnancy can reduce the risk of NSCL/P. We performed a family based association study in order to assess if a genetic variant of RFC1 could be involved in NSCL/P onset. We genotyped 404 unrelated probands and their relatives for three biallelic polymorphic variants (rs1051266, rs4818789 and rs3788205), that were selected because they produced conflicting results on previous investigations. Evidence of association was found between the investigated polymorphisms and NSCL/P in our sample of the Italian population, albeit with weak significance levels. Results from this investigation provided a support of previous studies suggesting a role of RFC1 in NSCL/P aetiology, reinforcing the concept that genetic predisposition to NSCL/P varies enormously within different ethnic groups.

Coating characteristics of dental implants such as composition and topography regulate cell response during implant healing. The aim of this study was to assess how surface topography can affect osteogenic differentiation of mesenchymal stem cells (MSCs) by analyzing the expression levels of bone-related genes and MSCs marker. Thirty disk-shaped, commercially pure Grade 2 titanium samples (10 × 2 mm) with 3 different surface topographies (DENTSPLY-Friadent GmbH, Mannheim, Germany) were used in the present study: 10 Ti machined disks (control), 10 Ti sandblasted and acid-etched disks (DPS(®)) and 10 sandblasted and acid-etched disks at high temperature (Plus(®)). Samples were processed for real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. By comparing machined and Plus(®) disks, quantitative real-time RT-PCR showed a significant reduction of the bone-related genes osteocalcin (BGLAP) and osteoblast transcriptional factor (RUNX2). The comparison between DPS(®) and Plus(®) disks showed a slight induction of all the genes examined (RUNX2, ALPL, COL1A1, COL3A1, ENG, FOSL1, SPP1, and SP7); only the expression of BGLAP remained stable. The present study, demonstrated that implant surface topography affects osteoblast gene expression. Indeed, Plus(®) surface produces an effect on MSCs in the late differentiation stages.

Unraveling of factors involved in multifactorial diseases is a great challenge. Different approaches can be contemplate and applied to a variety of congenital malformations. In the present investigation TFAP2A has been considered a good candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) aetiology, basing on a sum of considerations. TFAP2A has been seen involved in orofacial development in mice; it is located in the NSCLP candidate region 6p24; it codes for a transcription factor which regulates expression of IRF6, a gene implied in NSCLP; finally, it is embroiled in the branchiooculofacial syndrome, that includes clefting as feature. A family based association analysis was performed with a sample study of 405 NSCLP triads. Evidence of association was obtained with both single marker and haplotype analyses, thus providing a support for TFAP2A in NSCLP aetiology.

Objectives: Porous HA scaffolds are promising materials for tissue engineering because they offer a tridimensional support and serve as template for cell proliferation and at last tissue formation. Engipore provide a natural 3D scaffold with organic fibrous material in bone. However, how this material alters osteoblast activity to promote bone formation is poorly understood. Materials and methods: To study how Engipore can induce osteoblast differentiation in mesenchymal stem cells, the expression levels of bone related genes and mesenchymal stem cells marker were analyzed. Results: Engipore causes a significant induction of osteoblast transcriptional factors like SP7 and RUNX2 and of the bone-related gene osteocalcin (BGLAP).The expression of CD105 was not significantly changed in stem cells treated with Engipore with respect to untreated cells, while SSP1 (osteopontin) was significantly down expressed thus reducing osteoclast activity. Conclusions: The obtained results can be relevant to better understand the molecular mechanism of bone regeneration. Keywords: Stem cell, Biomaterial, Engipore, Differentiation, Bone

BACKGROUND: Although pulsed electromagnetic fields (PEMFs) are used to treat delayed unions and nonunions, their mechanisms of action are not completely clear. However, PEMFs are known to affect the expression of certain genes. QUESTIONS/PURPOSES: We asked (1) whether PEMFs affect gene expression in human osteoblastlike cells (MG63) in vitro, and (2) whether and to what extent stimulation by PEMFs induce cell proliferation and differentiation in MG-63 cultures. METHODS: We cultured two groups of MG63 cells. One group was treated with PEMFs for 18 hours whereas the second was maintained in the same culture condition without PEMFs (control). Gene expression was evaluated throughout cDNA microarray analysis containing 19,000 genes spanning a substantial fraction of the human genome. RESULTS: PEMFs induced the upregulation of important genes related to bone formation (HOXA10, AKT1), genes at the transductional level (CALM1, P2RX7), genes for cytoskeletal components (FN1, VCL), and collagenous (COL1A2) and noncollagenous (SPARC) matrix components. However, PEMF induced downregulation of genes related to the degradation of extracellular matrix (MMP-11, DUSP4). CONCLUSIONS AND CLINICAL RELEVANCE: PEMFs appear to induce cell proliferation and differentiation. Furthermore, PEMFs promote extracellular matrix production and mineralization while decreasing matrix degradation and absorption. Our data suggest specific mechanisms of the observed clinical effect of PEMFs, and thus specific approaches for use in regenerative medicine.

Porous polyethylene (PP or Medpor®) is an alloplastic material used worldwide for craniofacial reconstruction. Although several clinical studies are available, how this material alters osteoblast activity to promote bone formation is poorly understood. To study how PP can induce osteoblast differentiation in mesenchymal stem cells, the expression levels of bone related genes and mesenchymal stem cells marker were analyzed, using real time Reverse Transcription-Polymerase Chain Reaction. PP causes induction of osteoblast transcriptional factor RUNX2 and of the bone related genes osteocalcin (BGLAP) and alkaline phosphatase (ALPL). In contrast the expression of ENG was decreased in stem cells treated with PP respect to untreated cells, indicating the differentiation effect of this biomaterial on stem cells. The obtained results can be relevant to better understand the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects.