Naslov
Increased expression of Notch receptors on osteoclast progenitors induced by rheumatoid arthritis

Autori
Filipović, Maša ; Šućur, Alan ; Flegar, Darja ; Jajić, Zrinka ; Ikić Matijašević, Marina ; Lukač, Nina ; Kovačić, Nataša ; Kelava, Tomislav ; Šisl, Dino ; Zrinski Petrović, Katerina ; Katavić, Vedran ; Grčević, Danka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Annual meeting of the Croatian Immunological Society 2020: [programme and abstract book] / - Rijeka : Hrvatsko imunološko društvo, 2020, 33-33

Skup
Annual meeting of the Croatian Immunological Society 2020

Mjesto i datum
Online, 01.10.2020. - 02.10.2020

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
osteoclast progenitors ; colagen-induced arthritis ; rheumatoid arthritis ; notch

Sažetak
As Notch signaling has been implicated in osteoclast differentiation and activation, we investigated the expression of Notch receptors and ligands on osteoclast progenitors (OCP) in rheumatoid arthritis (RA) patients and mouse collagen-induced arthritis model. Peripheral blood mononuclear cells (PBMC) of RA patients and controls were phenotyped by flow cytometry, and an increase in Notch receptors on OCP was observed. During osteoclast differentiation in culture, there is an increase in Notch1, Notch3, Jag1 and DLL1 relative mRNA level in OCP, specifically in RA patients. By comparing the gene expression levels of Notch system components in sorted progenitors vs PBMC or synovial fluid cells we concluded that Notch receptors are generally more abundantly expressed on OCP, with an increase of Notch3 and DLL1 in arthritis. Likewise, in mice there is a significant increase in all the Notch receptors on flow cytometry, both in periarticular bone marrow (PBM) and spleen OCP. Although with initially higher levels of Notch1 and Notch2, during osteoclast differentiation levels of Notch3 and Notch4 as well as DLL4 mRNA increased in arthritic mice. Compared with controls, arthritic mice express more Notch2 mRNA in PBM. Immunohistochemistry of mice hind paws confirmed Notch receptor expression, with Notch1 and Notch2 on chondrocytes and synovial tissue, as well as Notch2 in PBM. Osteoclastogenic culture of sorted progenitors in wells coated with Notch ligands showed Jag1 inhibited, while DLL1 stimulated osteoclast formation. In conclusion, there is an increase in Notch expression on OCPs which may contribute to enhanced bone resorption in arthritis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
The work has been supported by Croatian Science
Foundation projects IP-2018-01-2414, UIP-2017-05-
1965 and DOK-2018-09-4276.

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