Altered human alveolar bone gene expression in type 2 diabetes—A cross‐sectional study

• Published in: Journal of periodontal research Vol. 57; no. 1; pp. 142 - 151
• Main Authors: Ayilavarapu, Srinivas, Doctor, Abbas, Lee, Chun‐Teh, Tribble, Gena D., Chiu, Yulun, Weltman, Robin L., Angelov, Nikola
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2022
• Subjects: Aged; Alveolar bone; Alveolar Bone Loss - genetics; Animal models; Animals; Bioinformatics; Bone and Bones; Bone growth; Bone healing; Bone morphogenetic protein 2; Bone morphogenetic protein 4; Bone morphogenetic protein 6; Bone resorption; Bone turnover; Cbfa-1 protein; Cross-Sectional Studies; Diabetes; diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - genetics; Gene Expression; Gene regulation; Homeostasis; Humans; Inflammation; Insulin-like growth factor I; Middle Aged; Osteogenesis; Patients; Periodontitis; RNA sequencing; rRNA; Sequence analysis; Transforming growth factor-b1; Wound healing; RNA sequencing; alveolar bone; diabetes mellitus; gene expression
• ISSN: 0022-3484; 1600-0765; 1600-0765
• DOI: 10.1111/jre.12947

Objective The objective of this cross‐sectional study is to investigate alveolar bone gene expression in health and diabetes through ribonucleic acid (RNA) sequencing and bioinformatics analysis. Background It is relatively unknown how type 2 diabetes modulates gene expression in alveolar bone in humans. Clinical concern regarding increased implant failure rate in patients with diabetes has been discussed in the literature. Previous studies in animal models and humans have suggested an imbalance between the genes regulating bone formation with data suggesting bone resorption in diabetes. However, there is lack of data regarding a comprehensive gene expression from human alveolar bone in diabetes. Methods Alveolar bone was collected from healthy and type 2 diabetic subjects undergoing periodontal and implant surgeries. The homogenized RNA sample was then extracted and analyzed for quantity and quality. RNA samples were further purified using ribosomal RNA depletion technique and processed for RNA sequencing and analysis. Expression levels for mRNAs were performed by calculating FPKM ([total_exon_fragments/mapped reads (millions) × exon length (kB)]), and differentially expressed mRNAs were selected with log2 (fold change) >1 or log2 (fold change) ≤1 and with a parametric F test comparing nested linear models. Results Eighteen bone samples (10 healthy, 8 patients with diabetes) were analyzed for gene expression. The mean age and HbA1c% of healthy versus diabetic subjects were as follows: age (55.3 ± 17.5 vs 63.9 ± 8.7 years) and HbA1c% (5.6 ± 0.29 vs 7.3 ± 2.4), respectively. Sequencing analysis showed that expression of genes that regulate bone turnover like TGFB1, LTBP4, IGF1, BMP2, BMP4, BMP6, SMAD1, RUNX2, MCSF, and THRA was significantly downregulated in diabetes samples compared with healthy controls with overall reduced expression of genes in the bone regulation pathway in patients with diabetes. Bioinformatics analysis for the altered genes highlighted several pathways related to bone homeostasis and inflammation in diabetes. Periodontitis did not affect the gene expression pattern based on diabetes status. Conclusions Altered expression of genes due to downregulation of certain pathways that are involved in bone turnover and inflammation suggests that overall wound healing and bone homeostasis may be compromised in type 2 diabetes.