Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction

Sen Yang; Yi-Ping Li; Wei Chen; Liang Hao; Matthew McConnell; Xuedong Zhou; Min Wang; Yan Zhang; John D. Mountz; Michael Reddy; Paul D. Eleazer

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Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction

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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 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 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 AAV-shRNA-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 acti-vation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.

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《骨研究（英文版）》 |2013年第3期|267-281|共15页
作者
Sen Yang; Yi-Ping Li; Wei Chen; Liang Hao; Matthew McConnell; Xuedong Zhou; Min Wang; Yan Zhang; John D. Mountz; Michael Reddy; Paul D. Eleazer;
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Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA;

Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA;

Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA;

Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA;

Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA;

The State Key Laboratory of 0ral Diseases, West China College of Stomatology, Sichuan University, Sichuan, P. R. China;

The State Key Laboratory of 0ral Diseases, West China College of Stomatology, Sichuan University, Sichuan, P. R. China;

Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA;

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA;

Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, Alabama, USA;

Department of Endodontics, University of Alabama at Birmingham, Birmingham, Alabama, USA;

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Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction

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