Hu Qiannan, Yang Lisa, Shan Zhongyan, Wen Shuqiong, Lu Huanzi, Zou Zhaolei, Guo Junyi, Liu Xiangqi, Xie Wenqiang, Cao Yang, Wang Zhi, Yang Le, Wang Xi
Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, China.
J Clin Periodontol. 2023 Feb;50(2):183-199. doi: 10.1111/jcpe.13724. Epub 2022 Oct 25.
The regulation of osteoclasts (OCs) by inhibitory immunoreceptors maintains bone homeostasis and is considered an important determinant of the extent of periodontal pathology. The aim of this study was to investigate the role of the inhibitory immunoreceptor CD300lf and its ligand ceramide in osteoclastogenesis in periodontitis.
The expression of CD300lf was measured in vitro and in a ligature-induced periodontitis model. The effect of CD300lf ablation on osteoclastogenesis was examined in ligature-retained and ligature removal periodontitis models. The effect of ceramide, the ligand of CD300lf, was examined in osteoclastogenesis in vitro and in vivo by smearing 20 μg of ceramide dissolved in carboxymethylcellulose on teeth and gingiva every other day in an experimental periodontitis model and ligature removal model.
CD300lf expression was downregulated during osteoclastogenesis. Ablation of CD300lf in the ligature-induced periodontitis model increased the number of OCs and exacerbated bone damage. Bone resorption caused by CD300lf ablation was reversible following ligature removal. CD300lf-ceramide binding suppressed osteoclastogenesis in vitro and inhibited alveolar bone loss in a mouse periodontitis model.
Our findings reveal that CD300lf-ceramide binding plays a critical negative role in alveolar bone loss in periodontitis by inhibiting OCs differentiation.
抑制性免疫受体对破骨细胞(OCs)的调节维持着骨稳态,被认为是牙周病理程度的一个重要决定因素。本研究的目的是探讨抑制性免疫受体CD300lf及其配体神经酰胺在牙周炎破骨细胞生成中的作用。
在体外和结扎诱导的牙周炎模型中检测CD300lf的表达。在结扎保留和结扎去除的牙周炎模型中研究CD300lf缺失对破骨细胞生成的影响。在实验性牙周炎模型和结扎去除模型中,通过每隔一天在牙齿和牙龈上涂抹20μg溶解于羧甲基纤维素的神经酰胺,研究CD300lf的配体神经酰胺在体外和体内对破骨细胞生成的影响。
在破骨细胞生成过程中,CD300lf表达下调。在结扎诱导的牙周炎模型中,CD300lf缺失会增加破骨细胞数量并加重骨损伤。结扎去除后,CD300lf缺失引起的骨吸收是可逆的。CD300lf-神经酰胺结合在体外抑制破骨细胞生成,并在小鼠牙周炎模型中抑制牙槽骨丧失。
我们的研究结果表明,CD300lf-神经酰胺结合通过抑制破骨细胞分化在牙周炎牙槽骨丧失中起关键的负性作用。