Objective: To compare the effects of artemisinin

dihydroartemisinin

artesunate and artemether on osteoclasts differentiation

and investigate relevant signaling pathways. Method: Osteoclast differentiation was induced by receptor activator of nuclear factor-κB(NK-κB) ligand (RANKL) in bone marrow-derived macrophages (BMMs). After different concentrations of artemisinin

dihydroartemisinin

artemether and artesunate were treated

tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells were observed by TRAP staining. TRAP

MMP-9 and cathepsin-K (Cts-K) mRNA expressions were detected by Real-time PCR

and TRAF6 and p65 protein expressions were detected by Western blot. Result: TRAP-positive multinucleated cells were successfully induced by RANKL

and TRAP

MMP-9 and Cts-K mRNA expressions

TRAF6 and p65 protein expression were significantly increased after treatment with RANKL. Importantly

artemisinin

dihydroartemisinin

artemether and artesunate could significantly reduce the number

nuclei and diameter of osteoclasts after induction with RANKL (P<0.05

P<0.01)

artemisinin obviously reduced TRAP mRNA expression (P<0.01)

dihydroartemisinin

artemether and artesunate significantly down-regulated the mRNA expressions of TRAP

MMP-9 and Cts-K(P<0.01)

and artemether and artesunate had a better therapeutic effect. In addition

the abnormal increase of TRAF6 and p65 proteins were obviously suppressed by artemisinin and artemisinin derivatives after induction with RANKL

and the results demonstrated that artesunate was the best one(P<0.01). Conclusion: Artemisinin and artemisinin derivatives could inhibit the effect of mouse BMMs in differentiating osteoclasts

which may be related to the down-regulation of TRAP

MMP-9 and Cts-K gene expressions

and the inhibition of TRAF6/NF-κB activation. The effect of artemether and artesunate is better than that of artemisinin and dihydroartemisininat at the same concentration.