ABSTRACT
Objective:To study the effects of deoxyadenosine(dAdo) on methotrexate (MTX) induced suppression of inflammatory bone destruction.Methods:The culture system of whole bone marrow cells (WBMCs) was utilized to evaluate osteoclastogenesis.TRAP staining and μCT analysis were utilized to evaluate osteoclastogenesis and bone destruction in adjuvant arthritis rats.Results:In the bone marrow culture system,MTX-induced suppression of osteoclastogenesis was abrogated by the addition of dAdo.dAdo canceled MTX-induced suppression of osteoclastogenesis in the rats with arthritis,and significantly abolished the therapeutic effects of MTX on inflammatory bone destruction in the rats.Conclusion:The accumulation of dAdo may be one cause of the losing effectiveness of MTX in bone destruction.
ABSTRACT
Objective:To study the mechanism of the effectiveness loss of methotrexate(MTX)in the treatment of rheumatoid arthri-tis.Methods:The culture system of rat whole bone marrow cells(WBMCs)and tartrateresistant acid phosphatase(TRAP)staining were utilized to evaluate osteoclastogenesis.The mRNA expression of osteoclastogenesis factors in the WBMCs culture system was examined by semi-quantitative RT-PCR.Results:Deoxyadenosine(dAdo)decreased MTX-induced suppression of osteoclastogenesis.The recov-ery effect of dAdo on MTX was partially prevented by caffeine.MTX significantly reduced mRNA expression of receptor activator of nu-clear factor kappa-B ligand(RANKL),dAdo partially recovered RANKL mRNA expression and inhibited osteoprotegerin(OPG)expres-sion.Conclusion:The accumulation of dAdo may induce the effectiveness loss of methotrexate in rheumatoid arthritis treatment.Com-bination of MTX and caffeine can be a potential therapeutic strategy.