Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products

Müller, Heinz-Dieter; Cvikl, Barbara; Janjić, Klara; Nürnberger, Sylvia; Moritz, Andreas; Gruber, Reinhard; Agis, Hermann (2015). Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products. Journal of endodontics, 41(11), pp. 1852-1861. Elsevier 10.1016/j.joen.2015.08.002

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INTRODUCTION Proangiogenic prolyl hydroxylase (PHD) inhibitors represent a novel approach to stimulate tissue regeneration. Diabetes mellitus involves the accumulation of advanced glycation end products (AGEs). Here we evaluated the impact of AGEs on the response of human pulp tissue to the PHD inhibitor L-mimosine (L-MIM) in monolayer cultures of dental pulp-derived cells (DPCs) and tooth slice organ cultures. METHODS In monolayer cultures, DPCs were incubated with L-MIM and AGEs. Viability was assessed based on formazan formation, live-dead staining, annexin V/propidium iodide, and trypan blue exclusion assay. Vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 production was evaluated by quantitative polymerase chain reaction and immunoassays. Furthermore, expression levels of odontoblast markers were assessed, and alizarin red staining was performed. Tooth slice organ cultures were performed, and VEGF, IL-6, and IL8 levels in their supernatants were measured by immunoassays. Pulp tissue vitality and morphology were assessed by MTT assay and histology. RESULTS In monolayer cultures of DPCs, L-MIM at nontoxic concentrations increased the production of VEGF and IL-8 in the presence of AGEs. Stimulation with L-MIM decreased alkaline phosphatase levels and matrix mineralization also in the presence of AGEs, whereas no significant changes in dentin matrix protein 1 and dentin sialophosphoprotein expression were observed. In tooth slice organ cultures, L-MIM increased VEGF but not IL-6 and IL-8 production in the presence of AGEs. The pulp tissue was vital, and no signs of apoptosis or necrosis were observed. CONCLUSIONS Overall, in the presence of AGEs, L-MIM increases the proangiogenic capacity, but decreases alkaline phosphatase expression and matrix mineralization.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > School of Dental Medicine, Restorative Dentistry, Research
04 Faculty of Medicine > School of Dental Medicine

UniBE Contributor:

Müller, Heinz-Dieter; Cvikl, Barbara and Gruber, Reinhard

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0099-2399

Publisher:

Elsevier

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

18 Feb 2016 09:36

Last Modified:

25 Jan 2017 12:15

Publisher DOI:

10.1016/j.joen.2015.08.002

PubMed ID:

26395911

Uncontrolled Keywords:

Advanced glycation end product, dental pulp, diabetes, interleukin, pulp regeneration, tissue engineering, vascular endothelial growth factor

BORIS DOI:

10.7892/boris.75638

URI:

https://boris.unibe.ch/id/eprint/75638

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