Inflammatory periodontal disease known as periodontitis is one of the most common conditions that affect human teeth and often leads to tooth loss. Due to the complexity of the periodontium, which is composed of several tissues, its regeneration and subsequent return to a homeostatic state is challenging with the therapies currently available. Cellular therapy is increasingly becoming an alternative in regenerative medicine/dentistry, especially therapies using mesenchymal stem cells, as they can be isolated from a myriad of tissues. Periodontal ligament stem cells (PDLSCs) are probably the most adequate to be used as a cell source with the aim of regenerating the periodontium. Biological insights have also highlighted PDLSCs as promising immunomodulator agents. In this review, we explore the state of knowledge regarding the properties of PDLSCs, as well as their therapeutic potential, describing current and future clinical applications based on tissue engineering techniques.
Background Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them. Material and Methods Articles published in the PubMed database from January 1999 and May 2020 were retrieved. Limitations of the studies and biological mechanisms were discussed. Results A total of 4,232 articles were found. Of these, 13 were analyzed according to inclusion criteria. Most papers found some association between periodontitis and HNC, although differences in periodontal evaluation, sample size, study design and tumor sites were observed. Porphyromonas gingivalis appears to increase the chance of both diseases, and it may be one of their main potential risk factors. Genetic predisposition is increased by exposure to environmental factors which can directly induce epigenetic changes that contribute to these diseases. Conclusions Understanding the mechanisms related to periodontitis and HNC has increased, however, well-designed clinical studies are needed for better conclusions. Furthermore, the advent of multiple "omic" technologies will help comprehend their possible association. Key words: Periodontitis, head and neck cancer, oral cancer, risk factors, biological factors.
Protease-activated receptor 1 (PAR1) has been associated to tissue repair and bone healing. The aim of the present study was to evaluate the effect of PAR1 activation on the osteogenic activity of human periodontal ligament stem cells (PDLSCs). PDLSCs were cultured in the presence of PAR1-selective agonist peptide (100 nM), thrombin (0.1 U/mL), or PAR1 antagonist peptide (100 nM). Calcium deposits, calcium concentration (supernatant), alkaline phosphatase activity (ALP), cell proliferation, and gene (qPCR) and protein expression (ELISA assay) of osteogenic factors were assessed at 2, 7, and 14 days. PAR1 activation led to increased calcium deposits (p<0.05), calcium concentration (p<0.05), ALP activity (p<0.05), and cell proliferation (p<0.05). Further, PAR1 activation may increase gene and protein expression of Runx2 (p<0.05) and OPG (p<0.05). In conclusion, PAR1 activation increases osteogenic activity of PDLSCs, providing a possible new strategy for periodontal regenerative therapies.
Human periodontal ligament stem cells (PDLSCs) have been studied as a promising strategy in regenerative approaches. The protease-activated receptor 1 (PAR 1 ) plays a key role in osteogenesis and has been shown to induce osteogenesis and increase bone formation in PDLSCs. However, little is known about its effects when activated in PDLSCs as a cell sheet construct and how it would impact bone formation as a graft in vivo. Here, PDLSCs were obtained from 3 patients. Groups were divided into control, osteogenic medium and osteogenic medium + PAR 1 activation by TFLLR-NH2 peptide. Cell phenotype was determined by flow cytometry and immunofluorescence. Calcium deposition was quantified by Alizarin Red Staining. Cell sheet microstructure was analyzed through light, scanning electron microscopy and histology and transplanted to Balb/c nude mice. Immunohistochemistry for bone sialoprotein (BSP), integrin β1 and collagen type 1 and histological stains (H&E, Van Giesson, Masson’s Trichrome and Von Kossa) were performed on the ex-vivo mineralized tissue after 60 days of implantation in vivo . Ectopic bone formation was evaluated through micro-CT. PAR 1 activation increased calcium deposition in vitro as well as BSP, collagen type 1 and integrin β1 protein expression and higher ectopic bone formation (micro-CT) in vivo.
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