Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Le

• 作 者: Sen Yang Liang Hao Matthew McConnell Xuedong Zhou Min Wang Yan Zhang John D Mountz Michael Reddy Paul D. Eleazer Yi-Ping Li Wei Chen
• 机 构: Department of Pathology, University of Alabama at Birmingham,Birmingham, Alabama, USA,The State Key
• 出 处: Bone Research
• 发表日期: 2013年03期
• 关键词: periodontal osteoclast gingivalis Inhibition cytokines impaired activate protect

Regulator of G-protein Signaling 10(Rgs10)plays an important function in osteoclast differentiation.However,the role of Rgs10 in immune cells and inflammatory responses,which activate osteoclasts in inflammatory 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 Rgs10’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 AAVshRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously.Our data indicate that Rgs10 may regulate dendritic cell proliferation and maturation,as well as the subsequent stimulation of T-cell proliferation and maturation,and osteoclast differentiation and activation.Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.

Regulator of G-protein Signaling 10 (Rgs10) plays an important function in osteoclast differentiation. Despite, the role of Rgs10 in immune cells and inflammatory responses, which activate osteoclasts in inflammatory lesions, such as bacteria-induced periodontal disease lesions, remains substantially unknown . In this study, we used an adeno-associated virus (AAV-) mediated RNAi (AAV-shRNA-Rgs10) knockdown approach to study Rgs 10’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. Reinforced, 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. Implantantly, AAV-mediated Rgs10 k nockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAVshRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously. Our data indicate that Rgs10 may regulate dendritic cell proliferation and maturation, as well as the subsequent stimulation of T-cell proliferation and maturation, and osteoclast differentiation and activation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.