Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction.
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-Rgs10mediatedRgs10knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption,in vitroandin vivo. Interestingly, local injection of AAV-shRNA-Rgs10into 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-mediatedRgs10knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAV-shRNA-Rgs10knockdown 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-Rgs10can be useful as a therapeutic treatment of periodontal disease.
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Sen
S
Yang
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Liang
L
Hao
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Matthew
M
McConnell
The State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Sichuan, P. R. China.
Xuedong
X
Zhou
The State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Sichuan, P. R. China.
Min
M
Wang
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Yan
Y
Zhang
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
John D
JD
Mountz
Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, Alabama, USA.
Michael
M
Reddy
Department of Endodontics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Paul D
PD
Eleazer
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Yi-Ping
YP
Li
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Wei
W
Chen
AAV-mediated RNAi knockdown; Rgs10; bone resorption; gene therapy; gingival inflammation; immune cell; periodontal disease