Basic ResearchEffects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products
Section snippets
Monolayer Culture of DPCs
Extracted third molars from nondiabetic patients without any sign of inflammation were used to harvest human DPCs after informed consent was obtained (Ethics Committee of the Medical University of Vienna, Vienna, Austria). Teeth were opened under sterile conditions, and pulp tissue was collected. DPCs were cultured in alpha-minimal essential medium (Invitrogen Corporation, Carlsbad, CA) supplemented with 10% fetal calf serum (PAA Laboratories, Linz, Upper Austria, Austria) and penicillin G at
DPCs Remain Vital When Incubated with AGEs in the Presence of L-MIM in Monolayer Cell Cultures
DPCs stimulated with AGE at 1, 10, and 100 μg/mL in the presence of L-MIM at 1 mmol/L showed no pronounced changes in formazan formation. No significant difference was observed when AGE-treated cells were compared with BSA-treated cells (Fig. 1A). Also, the addition of 10 ng/mL IL-1β made DPCs more susceptible to AGEs with regard to formazan formation (Fig. 1B). Staurosporine, which served as the positive control, reduced formazan formation at 30 and 100 nmol/L in the MTT assay (Fig. 1C).
Discussion
The dental pulp, as part of the dentin-pulp complex, is a highly vascularized tissue in which chronically dysbalanced blood glucose levels lead to the accumulation of AGEs in dentin (6). AGEs have been proposed to lead to compromised oral tissue regeneration 15, 16. Therefore, it is of relevance to assess the impact of AGEs on regenerative approaches. A novel experimental approach proposed for regenerative endodontics is the application of PHD inhibitors to stimulate revascularization and
Acknowledgments
The authors thank M. Pensch (Department of Oral Surgery, Medical University of Vienna, Vienna, Austria) for skillful technical assistance. The authors acknowledge S. Tangl and his team (Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Department of Oral Surgery, Medical University of Vienna, Vienna, Austria) and D. Teplanova and R. Szoeloesi (Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Vienna, Austria) for
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2022, Journal of Science: Advanced Materials and DevicesAlternative method for oral administration of insoluble toxins to rats. A prenatal study of L-mimosine
2021, ToxiconCitation Excerpt :Still, studies in laboratory animals with L-mimosine have also been carried out with the objective to better understanding its mechanisms of toxicity or even therapeutic action (Burawat et al., 2016, 2018; Chowtivannakul et al., 2016; Sergio et al., 2019; Husein et al., 2020). There are several other reports related to the possible pharmacological effects of L-mimosine, such as those obtained from endodontology as an inhibitor of prolyl hydroxylases with stimulation of angiogenesis and vascularization of the dental pulp (Müller et al., 2015; Trimmel et al., 2015); antiviral activity, in which L-mimosine mimics the actions of the anti-viral osetamivir (Tamiflu®), (Shan et al., 2012; Nguyen and Tawata, 2016); herbicidal activity (Smith and Fowden, 1966; Xuan et al., 2006); anti-inflammatory properties by selectively inhibiting COX-2 (Zebardast et al., 2009), among others; however, without a doubt, the biological action of L-mimosine most studied worldwide is that on the cell cycle, in which L-mimosine blocks the transition from phase G1 to S, stopping cell proliferation (Mosca et al., 1992; Moldovan et al., 2007). These studies have supported several others to combat the proliferative action of neoplastic cells (DeWys and Hall, 1973a; Chang et al., 1999, 2000).
L-mimosine and hypoxia enhance angiopoietin-like 4 production involving hypoxia-inducible factor-1alpha: Insights from monolayer and spheroid cultures of dental pulp-derived cells and tooth slice cultures
2018, Archives of Oral BiologyCitation Excerpt :Then DPC were incubated with either 1 mM L-MIM or hypoxia for 24 h. The dose was based on previous in vitro studies (Müller et al., 2015; Müller, Cvikl, Gruber, Watzek, & Agis, 2012). Hypoxia was induced based on an established assay shown previously with minor modifications (Gruber, Kandler, Agis, Fischer, & Watzek, 2008; Janjić, Lilaj, Moritz, & Agis, 2017; Janjić, Edelmayer, Moritz, & Agis, 2017).
Hypoxia-based strategies for regenerative dentistry—Views from the different dental fields
2017, Archives of Oral BiologyCitation Excerpt :New experimental techniques for regeneration of the dental pulp tissue involve strategies which are based on hypoxia signaling. HMA such as dimethyloxalylglycine, deferoxamine, l-mimosine, and CoCl2 increase intracellular levels of HIF-1α and stimulate VEGF production explanted dental pulp cells in vitro (Jiang et al., 2014; Müller et al., 2015; Müller, Cvikl, Gruber, Watzek, & Agis, 2012). This increase of VEGF was also found in tooth slice organ cultures which were treated with l-mimosine and also under simulated diabetes by the presence of advanced glycation end products (Müller et al., 2015).