Altered distribution of neutrophils and Nk cells in collagenase-induced osteoarthritis

Purpose/Objective: Osteoarthritis (OA) is a degenerative joint disease associated with high disability and pain. The aim of the present study is to evaluate the distribution and trafficking of neutrophils and NK cells in an experimental model of osteoarthritis. Materials and methods: SCID mice received an intra-articular (i.a) injection of collagenase at the knee joint (CIOA mice). In order to compare the progression of OA with an acute inflammatory process, a group of SCID mice were i.a. injected with zymosan (ZIA mice). The degree of joint damage were determined after H&E and toluidine blue staining. The distribution of neutrophils and NK cells and the expression of surface CXCR2, 4 and galectin-9 were evaluated in lymphoid organs and bodily fluids by flow cytometry at day 7 of the disease model. Results: Two populations of neutrophils, LY6Ghigh and LY6Glow were found in bone marrow (BM) and spleen. While BM LY6Ghigh cells expressed CXCR 2 and galectin-9, LY6Glow cells were negative for CXCR 2 and 4 but positive for galectin-9. Down-regulated expression of CXCR 2, 4 and galectin-9 on LY6Ghigh cells at day 7 of CIOA may correlate with the mobilization of these cells from the BM. CIOA NKp46 cells expressed CXCR4 and lost the surface CXCR2 in BM butin a lesser extent than ZIA population. In spleen, CXCR2 and 4 decreased on CIOA LY6Ghigh cells similarly to ZIA cells. LY6Glow population negative for CXCR2, 4 up-regulated galectin-9 only in CIOA mice suggesting its specific role in the osteoarthritic process. CIOA NKp46 cells in spleen down-regulated surface CXCR2 and 4. The percentages of CXCR 4+ cells in blood were strongly reduced in CIOA (for NK cells) and ZIA (for NK cells and neutrophils) groups suggesting that the cells with decreased expression of CXCR 4 can enter the circulation. A lot of the cells in ZIA synovial fluid were CXCR2+ and had down-modulated CXCR4 while CIOA phenotype was more similar to control. Conclusions: Our investigations shed a new light on the mechanism of LY6G neutrophils and NK cell trafficking in OA. Different modulations observed on these populations, suggest that the exploration of these mechanisms in OA could lead to the development of novel therapeutic strategies for the disease.