SAT0022 CXCL7 PROMOTES OSTEOCLASTOGENESIS IN RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by bone destruction[1]. Chemokine signaling by skeletal cells or by other cells of the bone marrow niche regulates bone formation and resorption[2]. Recent studies have found that CXCL7 enhanced the osteoclast formation in mouse bone marrow cells[3, 4]. Whether CXCL7 plays a role in human osteoclastogenesis especially in RA patients remains unclear. Objectives: To examine the functional role of CXCL7 in the induction of osteoclastogenesis in RA. Methods: The level of CXCL7 in CD14+ monocyte supernatant was assessed via enzyme-linked immunosorbent assay. Osteoclastogenesis of CD14+ monocyte from RA patients and healthy donors were evaluated by TRAP staining and F-actin ring immunofluorescence. Bone resorption pit was observed by scanning electron microscopy. We performed quantitative reverse transcription polymerase chain reaction (RT-PCR) to detect changes in osteoclast markers. RAW264.7 macrophages were also used to investigate specific signaling pathway by which CXCL7 stimulated during osteoclast formation. Results: CXCL7 level in CD14+ monocyte supernatant from RA patients (5690 ±627.05 pg/ml) was significantly higher than that in healthy controls (2301 ±535.52 pg/ml) (n=5, P Conclusion: CXCL7 level in CD14+ monocyte supernatant was higher in RA patients than that of healthy donors. CXCL7 promoted osteoclastogenesis in CD14+ monocyte both from RA patients and healthy donors. CXCL7 could be a potential therapeutic target for bone destruction in RA. References: [1] McInnes, I.B. and G. Schett, The pathogenesis of rheumatoid arthritis. N Engl J Med, 2011. 365(23): p. 2205-19. [2] Brylka, L.J. and T. Schinke, Chemokines in Physiological and Pathological Bone Remodeling. Front Immunol, 2019. 10: p. 2182. [3] Nakao, K., et al., IGF2 modulates the microenvironment for osteoclastogenesis. Biochem Biophys Res Commun, 2009. 378(3): p. 462-6. [4] Goto, Y., et al., CXCR4(+) CD45(-) Cells are Niche Forming for Osteoclastogenesis via the SDF-1, CXCL7, and CX3CL1 Signaling Pathways in Bone Marrow. Stem Cells, 2016. 34(11): p. 2733-2743. Acknowledgments : We gratefully thank the Medical Research Center of Peking University Third Hospital for providing experimental equipment and technical support. Disclosure of Interests: None declared