Dasatinib, a selective tyrosine kinase inhibitor, prevents joint destruction in rheumatoid arthritis animal model

Aim: We aimed to evaluate the preventive role of the tyrosine kinase inhibitor dasatinib in an animal model of rheumatoid arthritis (RA).

Methods: DBA/1J mice were injected with bovine type II collagen to induce arthritis (collagen-induced arthritis [CIA]). There were four experimental groups of mice, namely negative control (non-CIA), vehicle-treated CIA, dasatinib-pretreated CIA, and dasatinib-treated CIA. After collagen immunization, arthritis progression in the mice was clinically scored twice weekly for 5 weeks. Flow cytometry was used to evaluate in vitro CD4⁺ T-cell differentiation and ex vivo mast cell/CD4⁺ T-cell differentiation. Osteoclast formation was evaluated using tartrate-resistant Acid Phosphatase (TRAP) staining and by estimating the resorption pit area.

Results: We found that the clinical arthritis histological scores were lower in the dasatinib pretreatment group than in the vehicle and dasatinib post-treatment groups. Flow cytometry showed that FcεR1⁺ cells were downregulated and regulatory T cells were upregulated in splenocytes of the dasatinib pretreatment group compared with those in the vehicle group. Additionally, there was a decline in IL-17⁺ CD4⁺ T-cell differentiation and an increase in CD4⁺ CD24^high Foxp3⁺ T-cell differentiation with in vitro dasatinib treatment of human CD4⁺ T cells. The number of TRAP⁺ osteoclasts and the area of the resorption were decreased in the bone marrow cells derived from dasatinib-pretreated mice compared with those derived from vehicle group.

Conclusion: Dasatinib protected against arthritis in an animal model of RA by regulating the differentiation of regulatory T cells and IL-17⁺ CD4⁺ T cells and inhibiting osteoclastogenesis, indicating the therapeutic potential of dasatinib in the treatment of early RA.

dasatinib; osteoclast; regulatory T cell; rheumatoid arthritis; tyrosine kinase inhibitor.