Cordycepin Abrogates Methotrexate-Induced Suppression of Osteoclastogenesis

In this study, we have explored the reasons for the poor efficiency of 3′-deoxyadenosine in the treatment of rheumatoid arthritis. The effects of cordycepin and methotrexate on osteoclastogenesis were evaluated using the culture system of rat whole bone marrow cells and immunofluorescence staining with Kat1, a novel cell-surface antigen specifically expressed on rat osteoclasts. The effect of cordycepin on osteoclast formation was evaluated by tartaric acid-resistant phosphatase staining of bone marrow cell culture lines (pre-osteoclast formation lines) in which mesenchymal cells were removed. In the bone marrow culture system for evaluating osteoclastogenesis, methotrexate-induced suppression of osteoclastogenesis was abrogated only by the addition of cordycepin. In the pre-osteoclast formation system, cordycepin (3′-deoxyadenosine) was found to have no significant effect on osteoclast formation. To sum up, cordycepin should be carefully used in some cases of rheumatoid arthritis treated with methotrexate and in the severe stages of rheumatoid arthritis.