Naslov
Increased chemotaxis and activity of circulatory myeloid progenitor cells may contribute to enhanced osteoclastogenesis and bone loss in the C57BL/6 mouse model of collagen-induced arthritis

Autori
Ikić Matijašević, M. ; Flegar, D. ; Kovačić, N. ; Katavić, V. ; Kelava, T. ; Šućur, A. ; Ivčević, S. ; Cvija, H. ; Lazić Mosler, E. ; Kalajzić, I. ; Marušić, A. ; Grčević, D.

Izvornik
Clinical & Experimental Immunology (0009-9104) 186 (2016), 3; 321-335

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
bone loss, chemokines, collagen-induced arthritis, inflammation, osteoclast progenitors

Sažetak
Our study aimed to determine the functional activity of different osteoclast progenitor (OCP) subpopulations and signals important for their migration to bone lesions, causing local and systemic bone resorption during the course of collagen-induced arthritis in C57BL/6 mice. Arthritis was induced with chicken type II collagen (CII), and assessed by clinical scoring and detection of anti-CII antibodies. We observed decreased trabecular bone volume of axial and appendicular skeleton by histomorphometry and microcomputed tomography as well as decreased bone formation and increased bone resorption rate in arthritic mice in vivo. In the affected joints, bone loss was accompanied with severe osteitis and bone marrow hypercellularity, coinciding with the areas of active osteoclasts and bone erosions. Flow cytometry analysis showed increased frequency of putative OCP cells (CD3– B220– NK1.1–CD11b–/loCD1171CD1151 for bone marrow and CD3–B220–NK1.1–CD11b1CD1151Gr-11 for peripheral haematopoietic tissues), which exhibited enhanced differentiation potential in vitro. Moreover, the total CD11b1 population was expanded in arthritic mice as well as CD11b1F4/801 macrophage, CD11b1NK1.11 natural killer cell and CD11b1CD11c1 myeloid dendritic cell populations in both bone marrow and peripheral blood. In addition, arthritic mice had increased expression of tumour necrosis factor-a, interleukin-6, CC chemokine ligand-2 (Ccl2) and Ccl5, with increased migration and differentiation of circulatory OCPs in response to CCL2 and, particularly, CCL5 signals. Our study characterized the frequency and functional properties of OCPs under inflammatory conditions associated with arthritis, which may help to clarify crucial molecular signals provided by immune cells to mediate systemically enhanced osteoresorption.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA