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doctoral thesis
THE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS
2020. urn:nbn:hr:184:092101
Vidović Zdrilić, Ivana
University of Rijeka
Faculty of Medicine
Department of Endodontics and Restorative Dentistry

Cite this document

Vidović Zdrilić, I. (2020). THE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS (Doctoral thesis). Rijeka: University of Rijeka, Faculty of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:184:092101

Vidović Zdrilić, Ivana. "THE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2020. https://urn.nsk.hr/urn:nbn:hr:184:092101

Vidović Zdrilić, Ivana. "THE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2020. https://urn.nsk.hr/urn:nbn:hr:184:092101

Vidović Zdrilić, I. (2020). 'THE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS', Doctoral thesis, University of Rijeka, Faculty of Medicine, accessed 26 December 2024, https://urn.nsk.hr/urn:nbn:hr:184:092101

Vidović Zdrilić I. THE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS [Doctoral thesis]. Rijeka: University of Rijeka, Faculty of Medicine; 2020 [cited 2024 December 26] Available at: https://urn.nsk.hr/urn:nbn:hr:184:092101

I. Vidović Zdrilić, "THE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS", Doctoral thesis, University of Rijeka, Faculty of Medicine, Rijeka, 2020. Available at: https://urn.nsk.hr/urn:nbn:hr:184:092101

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TitleTHE ROLE OF αSMA< -EXPRESSING >PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS
Title (croatian)ULOGA αSMA PERIVASKULARNIH STANICA TIJEKOM STVARANJA TERCIJARNOG DENTINA
AuthorIvana Vidović Zdrilić
MentorAlen Braut (mentor)
Committee memberIvana Brekalo Pršo (predsjednik povjerenstva)
Committee memberIvica Anić (član povjerenstva)
Committee memberBojan Polić (član povjerenstva)
Committee memberAlen Braut (član povjerenstva)
GranterUniversity of Rijeka
Faculty of Medicine
(Department of Endodontics and Restorative Dentistry)
Rijeka
Defense date and country2020, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Dental Medicine
Universal decimal classification
(UDC)		616.31 - Stomatology
Thesaurus
(MESH - Medical Subject Headings)
Abstract
OBJECTIVES: The aim of this study was to examine the contribution of perivascular cells to odontoblasts during the development, growth, and repair of dentin and examine the effects of early and limited exposure of perivascular cells to fibroblast growth factor 2 (FGF2) in vivo using mouse molars as a model. MATERIAL AND METHODS: We used an inducible, Cre-loxP in vivo fate-mapping approach to examine the contributions of the descendants of cells expressing the αSMA-CreERT2 transgene to the odontoblast lineage. RESULTS: In vivo lineage-tracing experiments showed the contribution of αSMA-tdTomato+ cells to a small number of newly formed odontoblasts during primary dentinogenesis. Experiments revealed that mild injury to dentin first led to activation of aSMA-tdTomato+ cells in the entire pulp chamber. After their activation aSMAtdTomato+ cells migrated towards the site of injury, gave rise to pulp cells and a few odontoblasts that became integrated into the existing odontoblast layer expressing Col2.3- GFP and Dspp. Using an experimental pulp exposure model in molars to induce reparative dentinogenesis, we demonstrate the contribution of αSMA-tdTomato+ cells to cells secreting reparative dentin. Our results demonstrate that αSMA-tdTomato+ cells differentiated into Col2.3-GFP+ cells composed of both Dspp+ odontoblasts and Bsp+ osteoblasts. Early delivery of exogenous FGF2 to exposed pulp led to proliferative expansion of αSMA-tdTomato+ cells and their accelerated differentiation into odontoblasts. Results showed that the calcified bridge/reparative dentin in FGF2-treated pulps were lined with an increased number of Dspp+ odontoblasts and devoid of BSP+ osteoblasts. CONCLUSION: Our findings identify a population of mesenchymal progenitor cells capable of giving rise to a second generation of odontoblasts during reparative dentinogenesis. The increased number of odontoblasts derived from αSMAtdTomato+ cells and the formation of reparative dentin devoid of osteoblasts provide in vivo evidence for the stimulatory effects of FGF signaling on odontoblast differentiation from early progenitors in dental pulp.
Abstract (croatian)
CILJ ISTRAŽIVANJA: Reparativna dentinogeneza je regenerativni proces koji dovodi do stvaranja dentinskog mineraliziranog mosta koji pridonosi održavanju vitaliteta zubne pulpe. Reparativna dentinogeneza nastaje nakon intenzivne ozljede dentina koja dovodi do smrti odontoblasta i uključuje aktivaciju, proliferaciju i migraciju mezenhimnih matičnih stanica do mjesta ozljede i njihovu diferencijaciju u drugu generaciju odontoblasta i odontoblastima – sličnim stanica. Identitet stanica kćeri stanica i signalni putovi uključenih u proces reparativne dentinogeneze su još uvijek nedovoljno istraženi i nepoznati. Cilj ove studije je ispitati ulogu perivaskularnih stanica u pulpi koja eksprimira alfa aktin glatkog mišića-GFP (αSMA-GFP) u reparativnoj dentinogenezi i ispitati učinke FGF signalne molekule na ovu populaciju. Koristili smo inducirani CreloxP rekombinacijski sustav (αSMA-CreERT2) za eksperimente praćenja staničnih loza in vivo i in vitro. Cilj je ispitati doprinos perivaskularnih stanica odontoblastima tijekom razvoja, rasta i regeneracije dentina i ispitati učinke rane i ograničene izloženosti perivaskularnih stanica fibroblastičnom faktoru rasta 2 (FGF2) in vivo na uzorku mišjih kutnjaka. MATERIJALI I METODE: Koristili smo inducirani, Cre-loxP in vivo pristup praćenja sudbine stanica da bismo ispitali doprinos potomaka stanica koji izražavaju αSMA-CreERT2 transgen u odontoblastastičnoj liniji. REZULTATI: Pokusi in vivo praćenja loze na kutnjacima pokazali su doprinos αSMA-tdTomato+ stanica malom broju novoformiranih odontoblasta tijekom primarne dentinogeneze. Eksperimenti su otkrili da je blaga trauma dentina najprije dovela do aktivacije SMA-tdTomato+ stanica u cijeloj pulpnoj komori. Postotak područja koja zauzimaju SMA-tdTomato+ stanice u zubima sa traumom dentina bio je značajno veći nego kod zuba bez ozljeda. Nakon njihove aktivacije SMA-tdTomato+ stanice migrirale su prema mjestu ozljede, diferencirale u pulpne stanice, te su nekoliko SMA-tdTomato+ odontoblasta koji su se integrirali u postojeći odontoblastni sloj izražavali Col2.3-GFP i Dspp. Koristeći eksperimentalni model direktnog prekrivanja pulpe u kutnjacima kako bi potakli reparativnu dentinogenezu, prikazali smo doprinos αSMA-tdTomato+ stanica stanicama koje izlučuju reparativni dentin. Naši rezultati pokazuju da su se αSMA-tdTomato+ stanice diferencirale u Col2.3-GFP+ stanice, te su sastavljene od Dspp+ odontoblasta i Bsp+ osteoblasta. Rana primjena egzogenog FGF2 nakon direktnog prekrivanja pulpe dovela je do jače proliferacije αSMA-tdTomato+ stanica i njihove ubrzane diferencijacija u odontoblaste. Rezultati su pokazali da je mineralizirani most reparativng dentina u kutnjacima tretiranim FGF2-om obložen povećanim brojem Dspp+ odontoblasta uz odsudstvo BSP+ osteoblasta. ZAKLJUČAK: Blaga ozljeda dovela je do aktivacije perivaskularnih SMA-tdTomato+ stanica koje su diferencirale u stanice pulpe, kao i nekoliko odontoblasta koji su integrirani u prethodno postojeći sloj odontoblasta. Naši nalazi identificiraju populaciju mezenhimalnih potomskih stanica koje mogu stvoriti drugu generaciju odontoblasta (odontoblastima – slične stanice) tijekom reparativne dentinogeneze. Povećani broj odontoblasta dobivenih iz αSMA-tdTomato+ stanica i stvaranje reparativnog dentina lišenog osteoblasta pružaju in vivo dokaze za stimulacijske učinke signalizacije FGF2-a na diferencijaciju odontoblasta u zubnoj pulpi.
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:184:092101
Promotion2020
Study programmeTitle: Biomedicine Postgraduate (doctoral) study programme
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Public noteIspravan naslov rada: THE ROLE OF αSMA -EXPRESSING PERIVASCULAR CELLS DURING REPARATIVE DENTINOGENESIS
Created on2020-10-15 06:50:38