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Career situation of first and presenting author Resident. Introduction The underlying mechanism of excessive osteoclastogenesis causing bone erosion in rheumatoid arthritis (RA) remains elusive. PGC-1β is implicated in transcriptional regulation of osteoclastogenesis but its role in RA pathogenesis is unknown. Objectives To investigate whether PGC-1β regulated osteoclastogenesis in RA. Methods PGC-1β expression in peripheral CD14+ monocytes from RA patients were detected by immunofluorescence, flow cytometry and western blot. Peripheral CD14+ monocytes from RA patients or healthy controls were transfected with lentivirus for PGC-1β gene silencing or over-expression and cultured with M-CSF and RANKL. Mature osteoclasts and their bone resorption activity were determined by TRAP, F-actin and toluidine blue staining. DC-STAMP and bone degrading enzymes as well as signaling molecules were detected by western blot. Results Increased nuclear accumulation of PGC-1β was observed in peripheral CD14+ monocytes from RA patients and their relative PGC-1β protein expression was higher than that in healthy controls. Cultured with RANKL and M-CSF, the cell counts of mature osteoclasts on day 14 and 21 and the pit area of bone resorption lacunae on day 21 were significantly higher in RA patients than those in healthy controls. PGC-1β knockdown in monocytes suppressed the expression of cathepsin K, TRAP and MMP-9 as well as osteoclast differentiation and bone resorption activity, while PGC-1β over-expression markedly promoted these indicators and osteoclastogenesis. Furtherly, over-expressed PGC-1β increased the nuclear expression of NFATc-1. VIVIT, inhibitor of NFATc-1 activation, limited the effect of over-expressed PGC-1β on promoting the expression of cathepsin K, TRAP and MMP-9 in peripheral CD14+ monocytes from healthy controls. ChIP-QPCR analysis confirmed the immunoprecipitation of PGC-1β and the NFATc-1 promoter which indicated that PGC-1β binds to the NFATc-1 promoter region. Dual-luciferase reporter gene assay showed that over-expressed PGC-1β on the peripheral CD14+ monocytes from healthy controls increased the transcriptional activity of NFATc-1 in a dose-dependent manner. Conclusions Our data revealed a novel PGC-1β/NFATc-1 pathway contributing to excessive osteoclastogenesis in RA, which implied a potential therapeutic target of PGC-1β for osteoclast inhibition in RA. Acknowledgements This work was supported by National Natural Science Foundation of China (81471597, 81671612 and 81601427) and Guangdong Natural Science Foundation (2017A030313576 and 2017A030310236). Disclosure of Interest None declared.