These findings demonstrate that highly purified mesenchymal progenitor cell subsets can be obtained from the PDLs of both deciduous and permanent teeth, and further indicate phenotype dissimilarities that may have an impact on their clinical applications.

Aim: The objective of this study was to evaluate the effects of enamel matrix derivative (EMD), transforming growth factor‐β1 (TGF‐β1), and a combination of both factors (EMD+TGF‐β1) on periodontal ligament (PDL) fibroblasts. Material and methods: Human PDL fibroblasts were obtained from three adult patients with a clinically healthy periodontium, using the explant technique. The effects of EMD, TGF‐β1, or a combination of both were analysed on PDL cell proliferation, adhesion, wound healing, and total protein synthesis, and on alkaline phosphatase (ALP) activity and bone‐like nodule formation. Results: Treatment with EMD for 4, 7, and 10 days increased cell proliferation significantly compared with the negative control (p<0.05). At day 10, EMD and EMD+TGF‐β1 showed a higher cell proliferation compared with TGF‐β1 (p<0.01). Cell adhesion was significantly up‐regulated by TGF‐β1 compared with EMD and EMD+TGF‐β1 (p<0.01). EMD enhanced in vitro wound healing of PDL cells compared with the other treatments. Total protein synthesis was significantly increased in PDL cells cultured with EMD compared with PDL cells treated with TGF‐β1 or EMD+TGF‐β1 (p<0.05). EMD induced ALP activity in PDL fibroblasts, which was associated with an increase of bone‐like nodules. Conclusion: These findings support the hypothesis that EMD and TGF‐β1 may play an important role in periodontal regeneration. EMD induced PDL fibroblast proliferation and migration, total protein synthesis, ALP activity, and mineralization, while TGF‐β1 increased cellular adhesion. However, the combination of both factors did not positively alter PDL fibroblast behaviour.

Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas). In comparison to differentiated livers, hepatoblastomas exhibited a widespread and non-stochastic pattern of global low-level hypomethylation. The analysis revealed 1,359 differentially methylated CpG sites (DMSs) between hepatoblastomas and control livers, which are associated with 765 genes. Hypomethylation was detected in hepatoblastomas for ~58% of the DMSs with enrichment at intergenic sites, and most of the hypermethylated CpGs were located in CpG islands. Functional analyses revealed enrichment in signaling pathways involved in metabolism, negative regulation of cell differentiation, liver development, cancer, and Wnt signaling pathway. Strikingly, an important overlap was observed between the 1,359 DMSs and the CpG sites reported to exhibit methylation changes through liver development (p<0.0001), with similar patterns of methylation in both hepatoblastomas and fetal livers compared to adult livers. Overall, our results suggest an arrest at early stages of liver cell differentiation, in line with the hypothesis that hepatoblastoma ontogeny involves the disruption of liver development. This genome-wide methylation dysfunction, taken together with a relatively small number of driver genetic mutations reported for both adult and pediatric liver cancers, shed light on the relevance of epigenetic mechanisms for hepatic tumorigenesis.

PDL cells in association with GTR may significantly promote periodontal regeneration in class II furcation defects in dog.

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Background The developing periodontium is sensitive to local levels of phosphate (Pi) and pyrophosphate (PPi), as demonstrated by cementum phenotypes resulting from loss of function of protein regulators of Pi/PPi homeostasis. The progressive ankylosis protein (ANK) regulates transport of PPi, and Ank knock-out (KO) mice feature rapidly forming and thick cementum. We hypothesized that, besides affecting cementum formation, decreased extracellular PPi levels in Ank KO mice would also impact cementum regeneration. Methods Periodontal fenestration defects (2mm/1mm/0.5mm) were created on the buccal aspects of mandibular molars in Ank KO and wild-type (WT) mice. Mandibles were harvested at 15 and 30 days post-surgery for histology, histomorphometry, evaluation of in vivo fluorochrome labeling, and immunohistochemistry(IHC) for proteins including bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein 1 (DMP1), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). Results A greater amount of new cementum was observed for Ank KO mice at 15 and 30 days post-surgery (p<0.05), that was confirmed by fluorochrome labeling showing a higher new cementum appositional activity in the defect areas in Ank KO vs. controls. At days 15 and 30 during healing, regenerating cementum and associated cells in Ank KO recapitulated expression patterns mapped during development, including limited BSP and positive OPN and DMP1 in the cementum matrix, as well as elevated NPP1 in cementoblasts. Conclusions Within the limits of the study, these findings suggest that reduced local levels of PPi can promote increased cementum regeneration. Therefore, local modulation of Pi/PPi may be a potential therapeutic approach for achieving improved cementum regeneration.

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Background: The etiology of prenatal-onset short stature with postnatal persistence is heterogeneous. Submicroscopic chromosomal imbalances, known as copy number variants (CNVs), may play a role in growth disorders. Objective: To analyze the CNVs present in a group of patients born small for gestational age (SGA) without a known cause. Patients and methods: A total of 51 patients with prenatal and postnatal growth retardation associated with dysmorphic features and/or developmental delay, but without criteria for the diagnosis of known syndromes, were selected. Array-based comparative genomic hybridization was performed using DNA obtained from all patients. The pathogenicity of CNVs was assessed by considering the following criteria: inheritance; gene content; overlap with genomic coordinates for a known genomic imbalance syndrome; and overlap with CNVs previously identified in other patients with prenatal-onset short stature. Results: In 17 of the 51 patients, 18 CNVs were identified. None of these imbalances has been reported in healthy individuals. Nine CNVs, found in eight patients (16%), were categorized as pathogenic or probably pathogenic. Deletions found in three patients overlapped with known microdeletion syndromes (4q, 10q26, and 22q11.2). These imbalances are de novo, gene rich and affect several candidate genes or genomic regions that may be involved in the mechanisms of growth regulation. Conclusion: Pathogenic CNVs in the selected patients born SGA were common (at least 16%), showing that rare CNVs are probably among the genetic causes of short stature in SGA patients and revealing genomic regions possibly implicated in this condition.