Background The migration of osteoclast from circulation and bone marrow into bone surface has suggested as a novel therapeutic point for bone erosion in RA.
Objectives We explored the mechanisms involved in osteoclast migration.
Methods Gene expression profiling was identified by microarray analysis and validated by Real-time PCR during differentiation of bone marrow-derived macrophages (BMMs) into osteoclast (OCs). RANKL induced osteoclast precursor cell line RAW264.7 migration and invasion in the presence and absence of anti-CCL4 antibody was measured in vitro. Intracellular signaling pathway was assessed by Western blotting. Osteoclast formation was identified by TRAP staining.
Results A panel of 11 chemokines signal was significant increase in osteoclastic differentiation of BMMs by Microarray. High expression of CCL4 was validated in primary BMMs and RAW264.7 cell line during differentiated into OCs. RANKL induced osteoclast precursor cell migration and invasion was decreased upon addition of anti-CCL4 antibody. OCs formation and OCs related genes expression were not affected by CCL4 inhibition. Neutralization of CCL4 promoted the PI13K phosphorylation at 45 to 60min after RANKL stimulation in RAW264.7.
Conclusions CCL4 regulates RANKL-induced OCs migration, suggesting that CCL4 inhibition could be bone protective in RA
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Acknowledgements Support for this work was obtained from the National Natural Science Foundation of China (NSFC): 30701129 (WT), 30901332 (FW), 81172845 (WT), 81273294 (MZ), National Natural Science Foundation of Jiangsu province: BK2011851 (WT), BK2012875 (MZ), the special project of clinical medicine from Jiangsu province: BL2013034 (MZ), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and scholarship from Asia Pacific League of Associations for Rheumatology (APLAR) and International League of Associations for Rheumatology (ILAR) (WT).
Disclosure of Interest None declared