OPG inhibit the differentiation of osteoclasts through DOCK5 signal pathway

Rac1 is activated by DOCK5 which affect actin polymerization through PAK1,LIMK and Cofilin.It is confirmed that OPG(osteoprotegerin,OPG) have an effect on differentiation of osteoclasts,while its mechanism is not yet clear.Our research,with transmission electron microscope,real-time quantitative PCR and western blot,found that lamellipodium of osteoclast precursor cells was increased abnormally,transcription level of DOCK5 was decreased significantly,while PAK1,PAK2,PAK3,PAK1/2/3,LIMK2 and Cofilin protein expression and phosphorylation level of PA K1 Ser199/204 and PAK2 Serl92/197 sites had no change after treatment of 100 ng/mL OPG.Despite all this,phosphorylation of Ser144 /Thr423 in PAK1,Ser141/Thr402 in PAK2,Thr508 in LIMK1 and Thr505 in LIMK2 was decreased,however that of Cofilin was increased.These results indicate that OPG down regulate DOCK5 transcription,affect Rac1 activation,and decrease phosphorylation of Ser144 /Thr423 of PAK1 and Serl41/Thr402 of PAK2.And then decrease phosphorylation of Thr508