Naslov
Notch signal modulates phenotype and function of osteoclasts differentiated from common trilineage myeloid progenitor under inflammatory conditions

Autori
Grčević, Danka

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

Izvornik
8th International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems / Choi, Horowitz, Lorenzo, Ivashkiv, Nakamura, Shett, Sims, Takayanagi - Philadelphia, PA 19106, USA : Philadelphia, PA 19106, USA, 2022, 21-21

Skup
8th International Conference on Osteoimmunology: Interactions of the Immune and Skeletal Systems

Mjesto i datum
Kreta, Grčka, 21.05.2022. - 26.05.2023

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Notch, osteoclasts, macrophages, dendritic cells

Sažetak
Osteoclasts (OC), dendritic cells (DC) and macrophages (MA) may be derived from common trilineage myeloid progenitor of hematopoietic origin. Progenitor commitment is susceptible to regulation through Notch signaling. Moreover, Notch dysregulation has been implicated in a number of inflammatory diseases. We aimed to determine the effects of Notch signaling modulation on common progenitor commitment and functional properties of differentiated cells. We used CX3CR1CreERT2NICD1 (Cre+NICD1, overexpressed Notch 1 signal) and CX3CR1CreERT2RBPJκ (Cre+RBPJκ, silenced Notch signal) mice as a source of common bone marrow progenitor (CD45+CD3-B220-NK1.1-CD11bloCD115+). Cre recombinase, under the control of CX3CR1 promoter expressed in monocytes/macrophages, was induced in vitro by 4-hydroxytamoxifen. OCs differentiation was induced by M-CSF/RANKL ; MAs by M-CSF ; DCs by IL-4/GM-CSF ; inflammation by E. coli lipopolysaccharide. Functionally, DCs were tested for the ability to process and present antigen ; MAs to phagocytose E. coli particles, and OCs to resorb bone and express TRAP. Among tested lineages, Notch1 overexpression suppressed OC formation, whereas Notch deletion enhanced osteoclastogenesis, resulting in a greater number and larger osteoclasts. In accordance, RANK protein expression was upregulated in osteoclastogenic cultures from Cre+RBPJκ mice, as well as the gene expression of cFos and CatK. Notch modulation did not seem to affect the number of MAs or DCs. Functional assays under inflammatory conditions confirmed that Notch silencing amplifies antigen presentation by DCs and TRAP expression by OCs, whereas the effect on phagocytosis by MAs was less prominent. Although Notch signaling modulation affected functional properties of all three lineages, the major effect was observed in OCs, with enhanced differentiation and function by Notch signal silencing. Our results indicate that Notch signal participates in the regulation of OC activity in inflammatory diseases.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA