Osteogenic Potential of Mandibular vs. Long-bone Marrow Stromal Cells

Although fundamentally similar to other bones, the jaws demonstrate discrete responses to developmental, mechanical, and homeostatic regulatory signals. Here, we hypothesized that rat mandible vs. long-bone marrow-derived cells possess different osteogenic potential. We established a protocol for rat mandible and long-bone marrow stromal cell (BMSC) isolation and culture. Mandible BMSC cultures formed more colonies, suggesting an increased CFU-F population. Both mandible and long-bone BMSCs differentiated into osteoblasts. However, mandible BMSCs demonstrated augmented alkaline phosphatase activity, mineralization, and osteoblast gene expression. Importantly, upon implantation into nude mice, mandible BMSCs formed 70% larger bone nodules containing three-fold more mineralized bone compared with long-bone BMSCs. Analysis of these data demonstrates an increased osteogenic potential and augmented capacity of mandible BMSCs to induce bone formation in vitro and in vivo. Our findings support differences in the mechanisms underlying mandible homeostasis and the pathophysiology of diseases unique to the jaws

Zoledronate Impairs Socket Healing after Extraction of Teeth with Experimental Periodontitis

Osteonecrosis of the jaws (ONJ) is a rare but severe complication of antiresorptive medications, such as bisphosphonates, used in the treatment of bone malignancy or osteoporosis. Tooth extraction and dental disease have been strongly associated with ONJ development. Here, we investigated molecular and cellular markers of socket healing after extraction of healthy or teeth with experimental periodontitis (EP) in Wistar-Han rats treated with zoledronic acid (ZA). We included 4 experimental groups: vehicle-treated animals with extraction of healthy teeth or teeth with ligature-induced EP and ZA-treated animals with extraction of healthy teeth or teeth with EP. Animals were pretreated with vehicle or ZA for a week, and EP was induced. Four weeks later, the second maxillary molars were extracted; sockets were allowed to heal for 4 wk; animals were euthanized; and maxillae were isolated. Radiographically, extraction sockets in groups 1, 2, and 3 demonstrated normal healing. Contrary incomplete socket healing was noted after extraction of teeth with EP in ZA-treated rats of group 4. Histologically, persistent inflammation and extensive osteonecrosis were seen in group 4. Disorganization of the collagen network, collagen type III predominance, and lack of collagen fiber insertion in the necrotic bone were associated with impaired socket healing. Cells positive for MMP-9, MMP-13, and α-SMA expression were present at the areas of epithelial invagination and adjacent to osteonecrotic bone. Importantly, human biopsies from patients with ONJ showed similar findings. Our data emphasize the importance of dental disease and tooth extraction in ONJ pathogenesis and help delineate an altered profile in wound-healing markers during ONJ development. © 2017, © International & American Associations for Dental Research 2017

Genome-wide transcriptome analyses reveal p53 inactivation mediated loss of miR-34a expression in malignant peripheral nerve sheath tumours

Malignant peripheral nerve sheath tumours (MPNSTs) are aggressive soft tissue tumours that occur either sporadically or in patients with neurofibromatosis type 1. The malignant transformation of the benign neurofibroma to MPNST is incompletely understood at the molecular level. We have determined the gene expression signature for benign and malignant PNSTs and found that the major trend in malignant transformation from neurofibroma to MPNST consists of the loss of expression of a large number of genes, rather than widespread increase in gene expression. Relatively few genes are expressed at higher levels in MPNSTs and these include genes involved in cell proliferation and genes implicated in tumour metastasis. In addition, a gene expression signature indicating p53 inactivation is seen in the majority of MPNSTs. Subsequent microRNA profiling of benign and malignant PNSTs indicated a relative down-regulation of miR-34a in most MPNSTs compared to neurofibromas. In vitro studies using the cell lines MPNST-14 (NF1 mutant) and MPNST-724 (from a non-NF1 individual) show that exogenous expression of p53 or miR-34a promotes apoptotic cell death. In addition, exogenous expression of p53 in MPNST cells induces miR-34a and other miRNAs. Our data show that p53 inactivation and subsequent loss of expression of miR-34a may significantly contribute to the MPNST development. Collectively, our findings suggest that deregulation of miRNAs has a potential role in the malignant transformation process in peripheral nerve sheath tumours. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.MTG

Response of Shiraz grapevines to five different training systems in the Barossa Valley, Australia

Copyright © 2008 Australian Society of Viticulture and Oenology Inc.Own-rooted Shiraz, spaced 1.5 m apart in 2.75 m wide rows, were compared under five different training systems in the Barossa Valley, South Australia over five seasons starting 1995-96. Our objective was to determine how training affected fruit composition and crop yield in a context of efficient vineyard management. Training systems were: (i) low single wire (LSW), in which vines were trained to bi-lateral cordons, 1.0 m above the ground, non-shoot-positioned; (ii) high single wire (HSW), a higher cordon (1.8 m) version of LSW; (iii) vertically shoot positioned (VSP); (iv) Scott Henry, where canopies of alternate vines were cordon-trained and shoot-positioned upwards (SHU) or downwards (SHD); and (v) minimally pruned (MIN), the same as LSW, except vines were not annually spur-pruned. Crop yields (kg/m of row), over four seasons, averaged 4.9 (MIN), 2.9 (combined Scott Henry), 3.2 (VSP), 2.6 (HSW) and 2.9 (LSW). The greatest year-to-year variation in yield occurred with MIN and Scott Henry training. Crop weight of SHD vines was inferior to that of SHU vines in two seasons due to fewer shoots and bunches per vine, and to fewer bunches per shoot. Individual berry weights (g) were consistently least with MIN (0.89), and greatest with VSP (1.17). Fruit from all training systems exhibited similar rates of sugar accumulation during two seasons in which repeated measures of fruit maturation were made. Excepting the relatively light yields observed in 1999-2000, sugar accumulation was delayed in MIN vines, relative to other training systems, even when MIN harvest was delayed up to two weeks. The delay is most readily explained by the greater crops of MIN vines. Berry total anthocyanins and total phenolics concentrations (mg/g berry fresh wt.) at harvest were not greatly affected by training system. Berry anthocyanins and total phenolics exhibited a negative relationship with crop/m of canopy and a slight positive relationship with bunch exposure when evaluated across all training systems. Experimental plot soil depth and water availability affected cane pruning weights, yield per vine, berry weight, and canopy characteristics. LSW, HSW and MIN training systems all provided good yields of high quality fruit, although MIN did have a tendency to produce excessive crops in some years. VSP and Scott Henry training were less attractive due to their inherently greater canopy management requirements.Tony K. Wolf, Peter R. Dry, Patrick G. Iland, David Botting, Joy Dick, Ursula Kennedy and Renata Risti