Novi markeri za praćenje cijeljena kosti u bolesnika s prijelomom duge kosti

master's thesis

• Title (english): New markers for following bone healing in patients with long-bone fracture
• Author: Sara Medved
• Mentor: Slobodan Vukičević (mentor)
• Committee member: Donatella Verbanac (predsjednik povjerenstva)
• Committee member: Zdravko Petanjek (član povjerenstva)
• Committee member: Slobodan Vukičević (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Anatomy and Clinical Anatomy); Zagreb
• Defense date and country: 2014-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy

Abstract

Transformirajući čimbenik rasta beta (TGF-β) pripada velikoj superobitelji čimbenika rasta koji imaju važnu ulogu u mnogim fiziološkim i patološkim stanjima organizma, a djeluje na stanicu preko svojih receptora. TGF-β ima značajnu ulogu u proliferaciji epitelnih, endotelnih i hematopoetskih stanica te staničnoj diferencijaciji, cijeljenju rana, upali, angiogenezi i tumorogenezi. Mutacija TGF-β i njegovih receptora bitna je u patogenezi bolesti, posebno karcinoma. Uloga TGF-β prilikom razvoja i pregradnje kosti prikazana je u mnogim istraživanjima gdje se navedena molekula kod prijeloma kostiju navodi kao jedan od prvih čimbenika koji se može detektirati u krvi pacijenata. TGF-β III receptor (TGFβrIII) jedan je od najzastupljenijih receptora koji sudjeluje u djelovanju TGF-β na stanice. U zdravih ljudi TGFβrIII nije detektiran u plazmi, ali je pronađen u pacijenata s prijelomom dugih kostiju. Cilj ove studije je pratiti koncentraciju solubilnog TGFβrIII prilikom prijeloma dugih kostiju u ljudi, te utvrditi njegovu potencijalnu ulogu kao biomarkera u procesu koštanog cijeljenja. Istraživanje uključuje 22 pacijenata starija od 18 godina s dijagnozom jednostrukog koštanog prijeloma duge kosti traumatske naravi te 9 zdravih ispitanika bez ozljede koštanog sustava. Uzroci plazme prikupljeni su u različitim vremenskim periodima od trenutka prijeloma te tijekom redovitih kontrola, a zdravim ispitanicima tijekom sistematskog pregleda. Koncentracija TGFβrIII u prikupljenim uzorcima plazme određena je pomoću ELISA metode, te analizirana pomoću metode ograničene najveće vjerojatnosti REML. Dobivena koncentracija solubilnog TGFβrIII u zdravih ispitanika iznosi Ẋ= 40±10.7 pg/mL. Koncentracija solubilnog TGFβrIII nakon prijeloma postepeno raste, doseže svoj plato između 12. i 14. tjedna te zatim postupno pada na svoju početnu razinu krajem 25. tjedna. Studija je pokazala kako postoji izražaj TGFβrIII u plazmi zdravih pacijenata, te kako se koncentracija TGFβrIII prilikom cijeljenja kosti parabolično mijenja. Stoga je za zaključiti kako TGFβrIII možemo smatrati potencijalnim biomarkerom u cijeljenju kosti.

Abstract (english)

Transforming growth factor beta (TGF-β) belongs to a large growth factor superfamily having an important role in a number of physiologic and pathologic states of the organism, and it binds to the cell by means of its receptors. TGF-β has an important role in proliferation of epithelium, endothelium and hematopoietic cells and cell differentiation, wound healing, inflammation, angiogenesis and tumorigenesis. Mutation of TGF-β and its receptors is essential in pathogenesis of disease, especially carcinoma. The influence of TGF-β during bone formation and remodeling has been shown throughout many researches where the respective molecule in bone fracture is noted as one of primary factors able to be detected in patients’ blood. TGF-β III receptor (TGFβrIII) is among the most present receptors participating in action of TGF-β on cells. TGFβrIII is not detected in plasma of healthy people, but it has been found in patients with long bone fracture. The aim of this study is to monitor the concentration of soluble TGFβrIII during long bone fractures in humans and to determine its possible role as a biomarker in bone healing follow up. The study involved 22 patients aged 18 and above with the diagnosis of single long bone fracture induced by trauma and 9 healthy volunteers (no skeletal trauma). Plasma samples were taken in different temporal instants beginning with moment of fracture during regular control examinations and in healthy subjects during physical examination. TGFβrIII concentration in collected samples was determined using ELISA method, and was analyzed using REML method. Concentration of soluble TGFβrIII in healthy individuals amounts to Ẋ= 40±10.7 pg/mL. Concentration of soluble TGFβrIII after fracture rises steadily, reaching plateau between week 12 and 14, and then falls slowly to its initial value at the end of week 25. This study has shown that there is expression of TGFβrIII in plasma of healthy individuals and that concentration of TGFβrIII during bone healing exhibits parabolic change. It can be concluded therefore that TGFβrIII may be considered potential biomarker for bone healing.

• Keywords: TGFβrIII; betaglikan; biološki marker; prijelom kosti; cijeljenje
• Keywords (english): TGFβrIII; betaglycan; biological marker; bone fracture; fracture healing
• Language: croatian
• URN:NBN: urn:nbn:hr:105:671804
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2015-10-22 10:50:37