NOD2 contributes to Parvimonas micra‐induced bone resorption in diabetic rats with experimental periodontitis

• Published in: Molecular oral microbiology Vol. 39; no. 6; pp. 446 - 460
• Main Authors: Chen, Ying‐Yi, Tan, Li, Su, Xiao‐Lin, Chen, Ning‐Xin, Liu, Qiong, Feng, Yun‐Zhi, Guo, Yue
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.12.2024
• Subjects: Adult; Alkaline phosphatase; Alveolar bone; Alveolar Bone Loss - metabolism; Alveolar Bone Loss - microbiology; Animal models; Animals; Bacteria; Bone composition; Bone mass; Bone resorption; Computed tomography; Deactivation; Dental Plaque - microbiology; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - microbiology; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - microbiology; Differentiation (biology); Disease Models, Animal; Female; Glucose; Gum disease; Humans; Immunohistochemistry; Inflammation; Interleukin 6; Interleukin-12 - metabolism; Interleukin-6 - metabolism; Male; Microbiomes; Microbiota; Microorganisms; Middle Aged; NOD2 protein; Nod2 Signaling Adaptor Protein - metabolism; Nucleotides; nucleotide‐binding oligomerization domain 2; Oligomerization; oral microbiome; Osteoblastogenesis; Osteoblasts; Osteoblasts - metabolism; Osteogenesis; Periodontitis; Periodontitis - metabolism; Periodontitis - microbiology; Rats; Rats, Sprague-Dawley; Relative abundance; RNA, Ribosomal, 16S; Root resorption; rRNA 16S; type 2 diabetes mellitus; X-Ray Microtomography; alveolar bone; oral microbiome; type 2 diabetes mellitus; periodontitis; nucleotide‐binding oligomerization domain 2
• ISSN: 2041-1006; 2041-1014; 2041-1014
• DOI: 10.1111/omi.12467

Background Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide‐binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. Methods We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high‐throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro‐computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin‐12 (IL‐6) were detected by western blot. Results The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL‐6. Conclusions The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.