Aim:To study the effect of doxycycline (DOX) on osteoclastogenesis,matureosteoclast fate and function,wear particles-induced osteoeolysis,and to providesome foundation for treating aseptic loosening and osteolysis after jointarthroplasty.Methods:Osteoclasts were generated from mouse bone marrowmonocytes with the receptor activator of NF-kB ligand and the macrophage colonystimulating factor.DOX at a concentration of 5,10,15,and 20 μg/mL was respec-tively added to the medium.Seven days later,the osteoclasts were determinedthrough tartrate-resistant acid phosphatase (TRAP) staining.Mature osteoclastswere isolated from newborn rabbits and cultured for 3 d in 24-well plates or onbone slices.DOX at a concentration of 5,10,15,and 20 μg/mL was respectivelyadded to the medium.After TRAP staining,the osteoclasts were counted,resorp-tion on bone slices was quantified,and the area was calculated after toluidine blueand Mayer-hematoxylin staining.Polymethyl methacrylate (PMMA) or ultra-highmolecular weight polyethylene (UHMWPE) particles were implanted on thecalvariae of C57BL/J6 mice.DOX,at a dose of 2 and 10 mg·kg~(-1)·d~(-1),was respec-tively given intraperitoneally for 7 d.Seven days later,the calvariae were removedand processed for pathological analysis.Results:DOX treatment effectivelyinhibited in vitro osteoclastogenesis,affected the fate of mature osteoclasts,andinhibited mature osteoclasts,causing bone resorption.In vivo data indicated thatDOX strongly inhibited PMMA or UHMWPE-induced osteolysis andosteoclastogenesis.Conclusion:DOX can effectively inhibit osteoclastogenesisand affect mature osteoclast fate and suppress wear particles induced by osteoly-sis and osteoclastogenesis.DOX might be useful in the treatment or preventionof wear particles-induced osteolysis and aseptic loosening for its effect on osteo-clast generation and mature osteoclast fate and function. Aim: To study the effect of doxycycline (DOX) on osteoclastogenesis, mature osteoclast fate and function, wear particles-induced osteoeolysis, and to provide foundation foundation for treating a septic loosening and osteolysis after jointarthroplasty. Methods: Osteoclasts were generated from mouse bone marrowmonocytes with the receptor activator of NF-kB ligand and the macrophage colonystimulating factor. DOX at a concentration of 5, 10, 15 and 20 μg / mL was respecively added to the medium. Seven days later, the osteoclasts were determined through tartrate-resistant acid phosphatase (TRAP) staining. Characteristics of osteoclastswere isolated from newborn rabbits and cultured for 3 d in 24-well plates or onbone slices. DOX at a concentration of 5, 10, 15 and 20 μg / mL were respectivelyadded to the medium. After TRAP staining , the osteoclasts were counted, resorp-tion on bone slices was quantified, and the area was calculated after toluidine blue and Mayer-hematoxylin staining. Polymethyl methacrylate (PMMA) or ultra-highmolecu lar weight polyethylene (UHMWPE) particles were implanted on the calvariae of C57BL / J6 mice. DOX, at a dose of 2 and 10 mg · kg -1 d -1 was respecively administered intraperitoneally for 7 d. Seven days later, the calvariae were removed and processed for pathological analysis. Results: DOX treatment effectively inhibited in vitro osteoclastogenesis, affected the fate of mature osteoclasts, and inhibited mature osteoclasts, causing bone resorption. In vivo data indicated that DOX strongly inhibited PMMA or UHMWPE- induced osteolysis andosteoclastogenesis. Conlusion: DOX can effectively inhibit osteoclastogenesis and affect mature osteoclast fate and suppress wear particles induced by osteoly-sis and osteoclastogenesis. DOX might be useful in the treatment or prevention of wear particles-induced osteolysis and aseptic loosening for its effect on osteo- clast generation and mature osteoclast fate and function.