The influence of LPS and IL-33 on adult stem cells of periodontal ligament:functional changes and activated molecular mechanisms

Abstract

Contemporary methods for treating various diseases of the oral cavity, caused by congenital deformities, mechanical damage or damage caused by inflammatory or tumor diseases can be a complex clinical task, given that the requirement for restoration of function and aesthetics of the orofacial region is imposed. The supporting tissue of the tooth in which the tissue of the periodontium represents the connection between the teeth and the alveolar bone, has an important role in maintaining the structure and function of the orofacial system. The tissue of the periodontium is very rich with mesenchymal stem cells (MSC) and can be a suitable source of MSC population for potential therapeutic use. Due to periodontium damage, the establishment of teeth structure and function, and consequently the orofacial system, is very difficult, even with the application of the most modern prosthetic treatments. However, functional features оf MSC from periodontium (PD-MSC) have not been fully revealed, which is a necessary requirement for their application. A particularly important aspect is understanding of PD-MSC’s behavior in the inflammatory microenvironment, since the periodontium destruction is most often caused by periodontal disease, chronic inflammatory disease of the supporting tissue of the teeth that can lead to tooth loss. In addition, inflammation of the teeth supportive tissue may be an accompanying complication after the dental implant, which also indicates the need to improve existing prosthetic treatments. The aim of the research covered by this dissertation was to obtain data about effects of factors frequently associated with the periodontium niche on the functional properties of PD-MSC. The influence of LPS, as a strong initiator of the inflammatory process, on the regenerative and immunomodulatory PD-MSC was examined. On the molecular level mechanisms mediating the effects of LPS were determined, wherein the activity of MAPK (Mitogen-Activated Protein Kinases) signaling pathways was determined. In addition, the effect of IL-33, as an endogenous alarm signal, on the regenerative properties of PD-MSC was examined...

Savremeni načini lečenja različitih oboljenja usne duplje, nastalih usled urođenih deformiteta, mehaničkih oštećenja ili poremećaja uzrokovanim inflamatornim ili tumorskim oboljenjima mogu predstavljati kompleksan klinički zadatak s obzirom da se nameće zahtev obnove funkcije, ali i estetike orofacijalnog regiona. Značajnu ulogu u održanju strukture i funkcije orofacijalnog sistema ima potporno tkivo zuba u okviru koga tkivo periodoncijuma predstavlja vezu između zuba i alveolarne kosti. Tkivo periodoncijuma je bogato mezenhimskim matičnim ćelijama (MMĆ), te može biti pogodan izvor populacije MMĆ za potencijalnu terapijsku primenu. Usled oštećenja tkiva periodoncijuma uspostavljanje strukture i funkcije zuba, a time i orofacijalnog sistema je veoma otežano čak i uz primenu najsavremenijih protetskih tretmana. Ipak, funkcijske osobine MMĆ periodoncijuma (PD-MMĆ) nisu u potpunosti ispitane, što predstavlja neophodan uslov za njihovu primenu. Posebno važan aspekt predstavlja poznavanje ponašanja PD-MMĆ u inflamatornoj mikrosredini, budući da do razaranja tkiva periodoncijuma najčešće dolazi usled parodontopatije, hroničnog inflamatornog oboljenja potpornog tkiva zuba koje može dovesti do gubitka zuba. Pored toga, inflamacija potornog tkiva može biti prateća komplikacija nakon postavljanja dentalnih implantata što takođe ukazuje na potrebu za poboljšavanjem postojećih protetskih tretmana. Istraživanja obuhvaćena ovom disertacijom imala su za cilj dobijanje podataka o uticaju faktora koji se mogu naći u niši tkiva periodoncijuma na funkcijska svojstva PD-MMĆ. Ispitivan je uticaj LPS, kao snažnog inicijatora inflamatornog procesa, na regenerativna i imunomodulatorna svojstva PD-MMĆ...