miR‐124‐3p increases in high glucose induced osteocyte‐derived exosomes and regulates galectin‐3 expression: A possible mechanism in bone remodeling alteration in diabetic periodontitis

• Published in: The FASEB journal Vol. 34; no. 11; pp. 14234 - 14249
• Main Authors: Li, Jun, Guo, Yue, Chen, Ying‐Yi, Liu, Qiong, Chen, Yun, Tan, Li, Zhang, Shao‐Hui, Gao, Zheng‐Rong, Zhou, Ying‐Hui, Zhang, Gui‐Ying, Feng, Yun‐Zhi
• Format: Journal Article
• Language: English
• Published: United States 01.11.2020
• Subjects: Adult; Aged; Aged, 80 and over; alveolar bone; Alveolar Bone Loss - etiology; Alveolar Bone Loss - metabolism; Alveolar Bone Loss - pathology; Animals; Bone Remodeling; diabetes mellitus; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 2 - physiopathology; Exosomes - drug effects; Exosomes - genetics; Exosomes - metabolism; Female; Galectin 3 - genetics; Galectin 3 - metabolism; Gene Expression Regulation; Glucose - pharmacology; Humans; inflammation; Male; MicroRNAs - genetics; Middle Aged; osteoblast; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoblasts - pathology; Periodontitis - complications; Periodontitis - pathology; Rats; Rats, Sprague-Dawley; saliva; alveolar bone; saliva; diabetes mellitus; osteoblast; inflammation
• DOI: 10.1096/fj.202000970RR
• ISSN: 0892-6638

The mechanisms underlying the two‐way relationship between diabetes mellitus (DM) and periodontitis are unclear. We examined a possible effect of galectin‐3 (Gal‐3), a factor in DM and bone metabolism, on periodontitis with or without DM. Using enzyme‐linked immunosorbent assay, we detected saliva Gal‐3 in patients with periodontitis, with or without type 2 diabetes mellitus (T2DM). In animal models, we measured periodontal bone microarchitecture via micro computed tomography, and detected Gal‐3, Runt‐related transcription factor 2 (Runx2), and interleukin‐6 (IL‐6) expression in alveolar bone. Applying dual luciferase reporter assay, we explored the target binding of miR‐124‐3p and Gal‐3. We examined osteocyte‐derived exosomes with transmission electron microscopy and detected miR‐124‐3p, Gal‐3, and IL‐6 expression in exosomes. Saliva Gal‐3 was increased in DM compared with controls but decreased in patients with moderate periodontitis and DM compared with those who had moderate periodontitis only. Alveolar bone mass was increased in DM and exacerbated in DM with periodontitis. Gal‐3 and Runx2 were both increased in periodontitis and DM compared with controls, but decreased in DM with periodontitis compared with DM alone. MiR‐124‐3p targeted and inhibited Gal‐3 expression in vitro. Osteocytes secreted exosomes carrying miR‐124‐3p, Gal‐3, and IL‐6, which were influenced by high glucose. These findings indicate that osteocyte‐derived exosomes carrying miR‐124‐3p may regulate Gal‐3 expression of osteoblasts, especially under high‐glucose conditions, suggesting a possible mechanism for DM‐related alveolar bone pathologies.