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doctoral thesis
Signalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa
Zagreb: University of Zagreb, School of Medicine, 2023. urn:nbn:hr:105:162886
Filipović, Maša
University of Zagreb
School of Medicine

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

Cite this document

Filipović, M. (2023). Signalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:162886

Filipović, Maša. "Signalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa." Doctoral thesis, University of Zagreb, School of Medicine, 2023. https://urn.nsk.hr/urn:nbn:hr:105:162886

Filipović, Maša. "Signalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa." Doctoral thesis, University of Zagreb, School of Medicine, 2023. https://urn.nsk.hr/urn:nbn:hr:105:162886

Filipović, M. (2023). 'Signalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa', Doctoral thesis, University of Zagreb, School of Medicine, accessed 26 December 2024, https://urn.nsk.hr/urn:nbn:hr:105:162886

Filipović M. Signalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2023 [cited 2024 December 26] Available at: https://urn.nsk.hr/urn:nbn:hr:105:162886

M. Filipović, "Signalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:105:162886

Metadata
TitleSignalni put Notch osteoklastnih progenitora u mišjem modelu reumatoidnoga artritisa
Title (english)Notch signaling pathway of osteoclast progenitors in rheumatoid arthritis mouse model
AuthorMaša Filipović
MentorDanka Grčević (mentor)
Committee memberDora Višnjić (predsjednik povjerenstva)
Committee memberKrešo Bendelja (član povjerenstva)
Committee memberKristina Mlinac Jerković (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2023-02-28, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Human Physiology
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Neuroscience
Universal decimal classification
(UDC)		612 - Physiology
Abstract
Lokalni i sustavni gubitak kosti u reumatoidnom artritisu posljedica je pojačane aktivnosti osteoklasta. Cilj ovog rada bio je istražiti učinke modulacije signalnog puta Notch na diferencijaciju osteoklastnih progenitora (OCP) i razgradnju kosti u mišjem modelu artritisa potaknutog kolagenom. OCP mišje koštane srži (CD45+Ly6G−CD3−B220−NK1.1− CD11b−/loCD115+) i slezene (CD45+Ly6G−CD3−B220−NK1.1−CD11b+CD115+) podrijetla su mijeloidne loze, izražavaju kemokinski receptor CX3CR1 i njihov je udio povećan u artritisu. OCP izražavaju sva četiri receptora signalnog puta Notch, a u artritisu povećan je udio OCP koji izražavaju receptore Notch 2 i 3. Poticanje OCP ligandima signalnog puta Notch JAG1 i DLL1 dovodi do inhibicije osteoklastogeneze. Obrada neutralizacijskim protutijelima na receptore Notch 1 i 2 pojačala je osteoklastogenezu in vitro, a obrada miševa s artritisom in vivo dovela je do povećanja udjela OCP. Koristeći transgenični mišji soj s utišanim signalnim putem Notch u OCP (CX3CR1CreERT2/RBP-J) uočili smo pojačanu osteoklastogenezu, a u mišjem soju s aktiviranom signalizacijom putem receptora Notch 1 u OCP (CX3CR1CreERT2/NICD1) uočili smo smanjenu osteoklastogenezu. U artritičnih miševa s utišanim signalnim putem Notch u OCP potvrdili smo pojačanu diferencijaciju osteoklastnih progenitora i pojačanu koštanu razgradnju koja dovodi do smanjenog volumena mineralizirane kosti. Naši rezultati potvrđuju inhibicijsku ulogu signalnog puta Notch u diferencijaciji osteoklastnih progenitora u artritisu.
Abstract (english)
Periarticular and systemic bone loss in rheumatoid arthritis is mediated by increased osteoclast activity. We aimed to determine the effects of Notch signaling modulation on osteoclast progenitor (OCP) differentiation and arthritis-induced bone resorption in murine collagen-induced arthritis. Murine bone marrow and splenic OCPs, identified as CD45+Ly6G−CD3−B220−NK1.1−CD11b−/loCD115+ and CD45+Ly6G−CD3−B220−NK1.1− CD11b+CD115+ cells, respectively, derived from the myeloid lineage are specifically increased in arthritis and express the chemokine receptor CX3CR1. OCPs express all four Notch receptors and are susceptible to regulation through Notch signaling. In arthritis, we observed an increase in the frequency of OCPs expressing Notch 2 and 3. Stimulation with Notch ligand JAG1 and DLL1 results in inhibition of osteoclast differentiation, and treatment with neutralizing antibodies targeting Notch 1 and 2 results in increased osteoclastogenesis in vitro and increased frequency of OCPs in mice treated in vivo. We used transgenic mice with Notch signaling inhibition (CX3CR1CreERT2/RBP-J) or Notch 1 overexpression (CX3CR1CreERT2/NICD1) in OCPs and observed stimulated osteoclastogenesis with Notch deletion and reduced osteoclastogenesis with Notch 1 signal activation. Arthritic mice with inhibition of Notch signaling in OCPs had increased osteoclast differentiation and reduced talar bone volume. Our results confirm an inhibitory role of Notch signaling in osteoclast differentiation during arthritis.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:162886
Study programmeTitle: Biomedicine and Health Sciences
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
Extent115 str.
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2023-03-24 08:24:47