Objective:The novel cytokine interleukin (IL)-29 has been reported to induce antiviral, antitumor, and immune responses. However,the effect of IL-29 on osteoclast differentiation remains unclear. This study aimed to explore the effect of IL-29 on osteoclast differentiation and function in RANKL-induced in RAW264.7 cells (osteoclast precursors). Methods:The expression of IL-28Rα (specific receptor of IL-29) on RAW264.7 cells was evaluated by flow cytometry. RAW264.7 cells were stimulated with RANKL and different doses of recombinant IL-29 for 5 d,then the osteoclast formation was evaluated by counting multinucleated cells for tartrate-resistant acid phosphatase (TRAP) staining. Furthermore,the effect of IL-29 on the RANKL-induced expression of osteoclastic genes (TRAP,CTR and CTSK) and relevant genes(TRAF6 and RANK) was detected by real time PCR. Results:IL-29 inhibited the osteoclast formation in a dose-dependent manner in RANKL-induced RAW264.7 cells,and the dose of 100 ng/ml IL-29 significantly reduced the number of TRAP positive multinucleated cells and mRNA expression of osteoclastic genes (TRAP,CTR and CTSK) and relevant genes(TRAF6 and RANK). Conclusion:The findings in the present study indicate,for the first time,that IL-29 could inhibit osteoclast formation and function.