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doctoral thesis
Poremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti
Zagreb: University of Zagreb, School of Medicine, 2015. urn:nbn:hr:105:896297
Glasnović, Anton
University of Zagreb
School of Medicine

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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Glasnović, A. (2015). Poremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:896297

Glasnović, Anton. "Poremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti ." Doctoral thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:896297

Glasnović, Anton. "Poremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti ." Doctoral thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:896297

Glasnović, A. (2015). 'Poremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti ', Doctoral thesis, University of Zagreb, School of Medicine, accessed 26 November 2024, https://urn.nsk.hr/urn:nbn:hr:105:896297

Glasnović A. Poremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2015 [cited 2024 November 26] Available at: https://urn.nsk.hr/urn:nbn:hr:105:896297

A. Glasnović, "Poremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti ", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2015. Available at: https://urn.nsk.hr/urn:nbn:hr:105:896297

Metadata
TitlePoremećaji izražaja osteoresorptivnoga citokina RANKL u bolesnika s multiplom sklerozom na kliničkom početku bolesti
Title (english)Disturbed expression of the osteoresorptive cytokine RANKL in patients with multiple sclerosis at clinical onset
AuthorAnton Glasnović
MBZ: 291413
MentorDanka Grčević (mentor)
Committee membernije dostupno (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2015-06-18, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Multipla skleroza (MS, prema engl. multiple sclerosis) je autoimuna upalna bolest središnjeg živčanog sustava u čijoj patogenezi imunološki faktori čine glavni mehanizam demijelinizacijskog oštećenja. Također, bolesnici koji boluju od MS imaju poremećenu koštanu pregradnju, što se najčešće pripisuje primjeni glukokortikoida i smanjenoj pokretljivosti. Hipoteza ovoga istraživanja je da u bolesnika koji boluju od MS, osim tih sekundarnih čimbenika osteoporoze, postoji pojačano djelovanje RANKL (prema engl. receptor-activator of nuclear factor-B ligand)/RANK-signala u sklopu primarnog autoimunog poremećaja. Stoga smo analizirali parametre koštane pregradnje i upale u perifernoj krvi i cerebrospinalnom likvoru u MS na kliničkom početku bolesti u odnosu na profil osteoresorptivne RANKL/RANK-osovine. Na početku bolesti snižena je likvorska koncentracija neutralizacijskog receptora OPG (prema engl. osteoprotegerin), čime se povećava biološka dostupnost čimbenika RANKL. U uznapredovaloj bolesti povećan je omjer RANKL/OPG i izražaj aktivacijskog RANK-receptora u krvi, što odražava povećan proresorptivni potencijal. Profil čimbenika osovine RANKL/RANK/OPG povezan je s izražajem imunosupresivnih citokina IL-4 i IL-10 te proupalnih kemokina CCL2 i CXCL12. Izražaj osteoresorptivnog čimbenika RANKL pozitivno korelira, a neutralizacijskog receptora OPG negativno korelira s težinom bolesti i aktivnošću alkalne fosfataze, što može upućivati na povezanost aktivnosti osovine, intenziteta bolesti i koštane izgradnje. S obzirom da osovina RANKL/RANK/OPG sudjeluje u patogenezi i progresiji MS, ti čimbenika mogli bi služiti kao biomarkeri bolesti i ciljne molekule novijih terapijskih postupaka.
Abstract (english)
Multiple sclerosis (MS) is autoimmune inflammatory disease of the central nervous system in which immunological factors play the crucial role of demyelinating damage. Also, patients with MS have deregulated bone remodelling, mainly caused by glucocorticoid treatment and reduced mobility. We hypothesized that, beside these secondary osteoporotic factors, MS patients have enhanced RANKL (receptor-activator of nuclear factor-B ligand)/RANK-signal as a part of underlying autoimmune disturbance. Therefore we analyzed the parameters of bone remodeling and inflammation in peripheral blood and cerebrospinal fluid in MS patients at clinical onset in relation to osteoresorptive RANKL/RANK-axis. At MS clinical onset concentrations of decoy receptor OPG (osteoprotegerin) are decreased in cerebrospinal fluid, increasing the bioavailability of RANKL. Advanced MS is marked by higher RANKL/OPG ratio and activating RANK-receptor expression in peripheral blood, which suggests increased proresorptive potential. RANKL/RANK/OPG profile is associated with the expression of immunosuppressive cytokines IL-4 and IL-10 and proinflammatory chemokines CCL2 and CXCL12. Osteoresorptive factor RANKL is in positive, and decoy receptor OPG is in negative correlation with disease severity and alkaline phosphatase activity, interconnecting axis activity, disease intensity and bone formation. Since RANKL/RANK/OPG axis is involved in pathogenesis and progression of MS, these factors may serve as disease biomarkers and molecular targets of novel therapeutic approaches.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:896297
Study programmeTitle: Biomedicine and Health Sciences
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
Type of resourceText
Extent131 str.
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-05-05 07:41:53