Regulator of G-protein Signaling 10(Rgsl0)plays an important function in osteoclast differentiation.However,the role of Rgsl0 in immune cells and inflammatory responses,which activate osteoclasts in inflam-matory lesi...Regulator of G-protein Signaling 10(Rgsl0)plays an important function in osteoclast differentiation.However,the role of Rgsl0 in immune cells and inflammatory responses,which activate osteoclasts in inflam-matory lesions,such as bacteria-induced periodontal disease lesions,remains largely unknown.In this study,we used an adeno-associated virus(AAV-)mediated RNAi(AAV-shRNA-Rgs10)knockdown approach to study Rgsl0's function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease.We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption,in vitro and in vivo.Interestingly,local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells,T-cells and osteoclasts,and protected the periodontal tissues from local inflammatory damage and bone destruction.Importantly,AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines.Our results demonstrate that AAV-shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously.Our data indicate that Rgsl0 may regulate dendritic cell proliferation and maturation,as well as the subsequent stimulation of T-cell proliferation and maturation,and osteoclast differentiation and acti-vation.Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.展开更多
基金supported by NIH grants RC1DE-020533(Y.P.L.)and AR-055307(Y.P.L.)
文摘Regulator of G-protein Signaling 10(Rgsl0)plays an important function in osteoclast differentiation.However,the role of Rgsl0 in immune cells and inflammatory responses,which activate osteoclasts in inflam-matory lesions,such as bacteria-induced periodontal disease lesions,remains largely unknown.In this study,we used an adeno-associated virus(AAV-)mediated RNAi(AAV-shRNA-Rgs10)knockdown approach to study Rgsl0's function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease.We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption,in vitro and in vivo.Interestingly,local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells,T-cells and osteoclasts,and protected the periodontal tissues from local inflammatory damage and bone destruction.Importantly,AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines.Our results demonstrate that AAV-shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously.Our data indicate that Rgsl0 may regulate dendritic cell proliferation and maturation,as well as the subsequent stimulation of T-cell proliferation and maturation,and osteoclast differentiation and acti-vation.Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.
