Identification of Diagnostic Biomarkers of Osteoarthritis Based on Multi-Chip Integrated Analysis and Machine Learning
DNA AND CELL BIOLOGY
Authors: Zhang, Yueqi; Yang, Yi; Wang, Chenzhong; Wan, Shengcheng; Yao, Zhenjun; Zhang, Ying; Liu, Jinyu; Zhang, Chi
The pathogenesis of osteoarthritis (OA) is still unclear. It is therefore important to identify relevant diagnostic marker genes for OA. We performed an integrated analysis with multiple microarray data cohorts to identify potential transcriptome markers of OA development. Further, to identify OA diagnostic markers, we established gene regulatory networks based on the protein-protein interaction network involved in these differentially expressed genes (DEGs). Using support vector machine (SVM) pattern recognition, a diagnostic model for OA prediction and prevention was established. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that 190 DEGs were mainly enriched in pathways like the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, mitogen-activated protein kinase signaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, and osteoclast differentiation. Eight hub genes (POSTN,MMP2,CTSG,ELANE,COL3A1,MPO,COL1A1, andCOL1A2) were considered potential diagnostic biomarkers for OA, the area under curve (AUC) was >0.95, which showed high accuracy. The sensitivity and specificity of the SVM model of OA based on these eight genes reached 100% in multiple external verification cohorts. Our research provides a theoretical basis for OA diagnosis for clinicians.
Effects of diabetes on oxidative stress, periodontal ligament fiber orientation, and matrix metalloproteinase 8 and 9 expressions during orthodontic tooth movement
CLINICAL ORAL INVESTIGATIONS
Authors: Vicente, Ascension; Bravo-Gonzalez, Luis-Alberto; Navarro, J. A.; Buendia, A. J.; Camacho-Alonso, F.
Objectives To evaluate the influence of diabetes on oxidative stress, periodontal ligament (PDL) orientation, and matrix metalloproteinase (MMP) 8 and 9 expressions during orthodontic tooth movement in a rat model. Materials and methods An orthodontic appliance was placed in 60 Sprague-Dawley rats divided into three groups: normoglycemics (n = 20) and two streptozotocin-induced diabetic groups, one untreated (n = 20) and one insulin-treated (n = 20). At 24, 48, and 72 h and 1 week, rats were sacrificed. At each time point, myeloperoxidase (MPO) and malondialdehyde (MDA) were quantified by spectrophotometry, tooth movement was evaluated by micro-CT analysis, and hematoxylin and eosin staining was used to evaluate PDL fiber orientation and immunohistochemistry staining with semi-quantitative H-score analysis of MMP-8 and MMP-9 was performed.. Results At 24 h, MPO activity was significantly higher in untreated-diabetics than normoglycemics. At 24 and 48 h, the MDA level in untreated-diabetic rats was significantly higher than in normoglycemics and insulin-treated animals. At 72 h and 1 week, PDL fibers were oriented significantly more irregularly in untreated-diabetics than in normoglycemics. At all time points, MMP-8 and MMP-9 expressions were significantly higher in both diabetic groups than in the normoglycemic group. After the second day, tooth movement was significantly greater in untreated-diabetics than in the insulin-treated and normoglycemic groups. Conclusions Mechanical stress in untreated-diabetic rats produces more inflammatory response, oxidative stress, tooth movement, PDL disorganization, and MMP-8 and MMP-9 expressions than among normoglycemics. Insulin reverses these effects, favoring the reorganization of periodontal ligament.