Naslov
Effect of anti‐Notch 1 neutralizing antibody on the activity of human and mouse osteoclast progenitors stimulated by Notch‐ligands DLL1 and JAG1

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

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

Izvornik
European journal of immunology, 51 (2021), Suppl 1 / - , 2021, 388-388

Skup
6th European congress of immunology (ECI 2021)

Mjesto i datum
Online, 01.09.2021. - 04.09.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
animal models ; autoimmunity ; cell signalling ; myeloid cells ; rheumatoid arthritis

Sažetak
Bone loss associated with rheumatoid arthritis (RA) is caused by enhanced osteoclast differentiation and function. We aimed to determine the Notch receptor profile on human and mouse osteoclast progenitors (OCP) and the effect of Notch receptor signaling inhibition on OCP activity in murine collagen‐induced arthritis (CIA) and human RA samples. Peripheral blood was collected from RA patients. Periarticular bone marrow (PBM) and spleen (SPL) were harvested from mice with CIA, additionally treated by i.p. injections of anti‐Notch 1 neutralizing antibodies (1 mg/kg). FACS sorted OCPs were stimulated by osteoclastogenic factors (M‐CSF/RANKL), in Jagged (JAG)1 or Delta‐like (DLL)1 coated wells, with or without anti‐ Notch 1 neutralizing antibodies. The research was approved by the Ethics Committee. Both mouse (CD45+CD11blo/+CD115+CCR2+ or CCR2lo) and human (CD45+CD11b+CD14+CCR2+) OCPs express Notch receptors, with Notch 1 and 2 being the most abundantly detected. In vitro stimulation with DLL1 significantly increased, while stimulation with JAG1 significantly decreased osteoclastogenesis. The addition of anti‐Notch 1 to ligand‐stimulated OCPs resulted in an increased number of TRAP+ osteoclasts, partially reversing JAG1 inhibition. Both PBM and SPL OCPs from mice in vivo treated with anti‐Notch 1 produced a higher number of TRAP+ osteoclasts, with increased expression of osteoclast differentiation genes. Our results confirm that Notch signaling regulates osteoclast differentiation, with DLL1 exhibiting a stimulatory, and JAG1 a suppressive role. Anti‐ Notch 1 neutralizing antibodies partially reversed suppression by JAG1, proposing Notch 1/JAG1 pathway as a possible therapeutic target for the regulation of osteoclast activity in arthritis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA