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

中文翻译：

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抑制 Rgs10 表达可防止细菌诱导的炎症性病变和破骨细胞介导的骨破坏中的免疫细胞浸润。

G 蛋白信号调节剂 10 (Rgs10) 在破骨细胞分化中起重要作用。然而，Rgs10 在免疫细胞和炎症反应中的作用，在炎症损伤中激活破骨细胞，如细菌诱导的牙周病损伤，在很大程度上仍然未知。在这项研究中，我们使用腺相关病毒 (AAV-) 介导的 RNAi (AAV-shRNA-Rgs10) 敲低方法来研究 Rgs10 在牙周病小鼠模型中细菌诱导的炎症病变中的免疫细胞和破骨细胞中的功能。我们发现 AAV-shRNA-Rgs10 介导的 Rgs10 敲低会在体外和体内损害破骨细胞生成和破骨细胞介导的骨吸收。有趣的是，将AAV-shRNA-Rgs10局部注射到细菌诱导的炎症病变的牙周组织中，大大减少了树突细胞、T细胞和破骨细胞的数量，保护了牙周组织免受局部炎症损伤和骨质破坏。重要的是，AAV 介导的 Rgs10 敲低也降低了破骨细胞标志物和促炎细胞因子的局部表达。我们的结果表明，牙周病组织中的 AAV-shRNA-Rgs10 敲低可以同时预防骨吸收和炎症。我们的数据表明，Rgs10 可能调节树突细胞增殖和成熟，以及随后刺激 T 细胞增殖和成熟，以及破骨细胞分化和激活。