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.
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 micro-computed 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-/loCD117+CD115+for bone marrow and CD3-B220-NK1.1-CD11b+CD115+Gr-1+for peripheral haematopoietic tissues), which exhibited enhanced differentiation potential in vitro. Moreover, the total CD11b+population was expanded in arthritic mice as well as CD11b+F4/80+macrophage, CD11b+NK1.1+natural killer cell and CD11b+CD11c+myeloid dendritic cell populations in both bone marrow and peripheral blood. In addition, arthritic mice had increased expression of tumour necrosis factor-α, 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.
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.|Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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Ikić Matijašević
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.|Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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Flegar
Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.|Department of Anatomy, University of Zagreb School of Medicine, Zagreb, Croatia.
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Kovačić
Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.|Department of Anatomy, University of Zagreb School of Medicine, Zagreb, Croatia.
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Katavić
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.|Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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Kelava
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.|Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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Šućur
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.|Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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Ivčević
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.|Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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Cvija
Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.|Department of Anatomy, University of Zagreb School of Medicine, Zagreb, Croatia.
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Lazić Mosler
Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA.
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Kalajzić
Department of Research in Biomedicine and Health, University of Split School of Medicine, Split, Croatia.
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Marušić
Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb, Croatia.|Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
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http://orcid.org/0000-0002-2365-8249
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Grčević
D000818:Animals; D001169:Arthritis, Experimental / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D001323:Autoantibodies / Q000276:immunology; D015415:Biomarkers; D001706:Biopsy; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D002454:Cell Differentiation; D002633:Chemotaxis / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D010641:Phenotype; D055114:X-Ray Microtomography
D001323:Autoantibodies; D015415:Biomarkers; D024043:Collagen Type II; D016207:Cytokines
bone loss; chemokines; collagen-induced arthritis; inflammation; osteoclast progenitors