AB0035 CHEMOKINES (IL-8 & GRO-Α) AND CXCR1/2 PATHWAY INDUCES SENESCENCE INDUCTION IN CHONDROCYTES

Background Tumor Necrosis Factor-α(TNF- α) and Interleukin(IL-1) are well-known in the induction of senescence chondrocytes play an important role pathogenesis Osteoarthritis (OA). However, targeting these pathways has not yielded promising results. The chemokines IL-8(CXCL8) Gro-α(CXCL1), as well CXCR1/2 pathways, known to mediate inflammation apoptosis. precise OA is unknown. We hypothesize that signaling pathway involved chondrocytes. Objectives To evaluate derived from patients with healthy cell. Methods Healthy primary chondrocytes(HPC) cell lines human chondrocyte cells diagnosed cultured expanded up passage 5. Cells were induced IL-8 GRO–a followed by determining marker via β -galactosidase(β-GAL, histochemical staining) UPAR P16NKa using qRT-PCR. Apoptosis both HPCs OPCs done Annexin V Proprium iodide (PI) Flow-cytometry. Statistical analysis was performed un-paired t test One-way-Anova. Results This study showed % β-GAL HPC almost negligible. significantly higher OPC( p<0.001 ). Moreover, when stimulated IL-8, exhibited markedly increase positive blue a time dependent manner (p< 0.001 )(at 24 hrs., 48 72 hrs. & 96 hrs.). In line results OPC also Gro- α hrs.,72 hrs {Figure 1(A)(B)(C)}. Since TNF-α IL1-β reported have chondrocytes, we examined treated found significant no. stained (Table 1 These further validated fold change expression genes at manner. observed ( p=0.01 ); p=0.03 ) HPC. stimulation Gro-α manner(at 48hrs., 72hrs. hrs.) HPCs. Similarly, hrs.( p=0.69 p=0.05 p<0.0001 Gro–α While Flow-cytometric revealed negative for apoptotic markers viz., PI. Conclusion Overall, this highlights induce key event OA. CXCR2 may be explored therapeutic potential. Reference [1]Cecil DL, Rose DM, Terkeltaub R, Liu-Bryan R. Role interleukin-8 PiT-1 CXCR1-mediated inorganic phosphate uptake Arthritis Rheumatism: Official Journal American College Rheumatology. 2005 Jan;52(1):144-54. Table 1. mean ± SD Time (Hrs.) C 2.959±2.131 3.563±1.627 2.402±2.110 2.817±2.279 14.602±12.411 17.7893±6.808 36.808±5.314 46.956±16.709 10.112±4.420 19.328±5.840 34.544±9.813 47.852±13.321 14.496±16.698 20.731±8.859 38.899±11.321 50.712±13.865 11.283±3.926 18.944±5.945 34.279±5.812 32.445±11.695 12.890 3.2101 14 6.309 13.094± 4.909 15.098± 3.980 19.614 3.3804 43.614 10.301 66.234± 9.026 77.162± 10.936 18.021 4.092 67.814 11.3041 76.414± 5.024 83.112 4.936 18.978±4.098 54.627 8.337 79.902± 8.673 88.782±10.352 14.141±9.018 56.982 9.378 77.834±6.342 89.342±7.892 Figure Acknowledgements Anamika Kumari Anuja acknowledges Department Biotechnology, Ministry Science Technology, Government India her DBT -JRF/SRF -programme fellowship. Intramural Research Grant, SGPGIMS, Lucknow. Disclosure Interests None Declared.