The mevalonate pathway (MVP) and the anti-angiogenic effect of bisphosphonates have been shown to play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study determined the effect of the bisphosphonate, zoledronic acid and the replenishment of the MVP by geranylgeraniol on human gingival fibroblasts. Cell viability, apoptosis, morphological analysis using transmission electron microscopy, and gene expression for vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B, epiregulin and interferon-alpha were conducted. Results showed cellular viability was decreased in the presence of zoledronic acid and the co-addition of zoledronic acid with geranylgeraniol restored cell viability to control levels. Caspase 3/7 was detected in zoledronic-acid-treated cells indicating apoptosis. Transmission electron microscopy revealed dilation of the rough endoplasmic reticulum with zoledronic acid and the appearance of multiple lipid-like vesicles following the addition of geranylgeraniol. Zoledronic acid significantly (P < 0.05, FR > ± 2) up-regulated vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B and epiregulin at one or more time points but not interferon-alpha. Addition of geranylgeraniol resulted in a reduction in the expression of all five genes compared with zoledronic-acid-treated human gingival fibroblasts. The study concluded geranylgeraniol partially reversed the effects of zoledronic acid in human gingival fibroblasts both at the cellular and genetic levels, suggesting the regulation of these genes is mediated via the mevalonate pathway.
New Zealand has a long history of dental care provided by school dental nurses, now known as dental therapists. The nature of their training courses, although delivered in different centers, had remained relatively constant until 1999 when educational responsibility was transferred to the universities. Dental hygienists were not trained in New Zealand until 1994, with the exception of the New Zealand Army hygienists. Since 2001, the education of both dental therapists and dental hygienists has been the responsibility of the universities. Significant and progressive changes in educational delivery have occurred since then, which have culminated in three-year degree qualifications for dual-trained oral health professionals. Factors influencing this change included increased professionalism associated with the new legislative requirements for registration, workforce shortages, and enhanced educational and clinical practice requirements. The Bachelor of Oral Health degree at the University of Otago has an added emphasis on social sciences and incorporates aspects of learning relating to New Zealand's cultural heritage.
As the only known
mammalian organ that can fully and annually regenerate,
deer antler has significant advantages over lower-order animal models
when investigating the control of stem-cell-based organ regeneration.
Antler regeneration is known to be initiated and maintained by neural-crest-derived
stem cells in different states of activation. Antler stem cells can
therefore be used as a model to study proteins and pathways involved
in the maintenance of a stem cell niche and their activation and differentiation
during organ formation. In this study, the MSC markers CD73, CD90,
and CD105 were examined within the antler tip. Label-free quantification
was performed to investigate the protein profiles of antler stem cells
under different stages of activation and included dormant pedicle
periosteum (DPP), antler growth center (GC), post-active stem cells
from mid-beam antler periosteum (MAP), and deer facial periosteum
(FP) as a control (n = 3 per group). PEAKS and IPA
software were used to analyze the proteomic data. Our research confirmed
the central role of stem cell activation in the development of this
mammalian organ by localizing the MSC markers within the antler growth
center. Label-free quantification revealed that the greatest number
of unique proteins (87) was found in the growth center. There were
only 12 proteins found with expression levels that significantly differed
between DPP and FP. Protein profiles of these two groups indicated
that antler stem cells may use similar mechanisms to maintain dormancy
within a stem cell niche. The number of significantly regulated proteins
among DPP, MAP, and GC was 153. Among them, the majority were upregulated
in the growth center. Activation of antler stem cells was associated
with many biological processes and signaling pathways, such as Hippo
and canonical Wnt signaling. This work identifies the key pathways,
molecular/cellular functions, and upstream regulators involved in
mammal organ regeneration. The mass spectrometry proteomics data have
been deposited to the ProteomeXchange
Consortium via the iProX partner repository with the dataset
identifier PXD016824.
Based on the findings of this study, we suggest that the source of low levels of IL17A in periodontal tissues is mast cells not Th17 cells and that Tregs may have a more prominent role in the pathogenesis of periodontal disease than Th17 cells.
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