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Purpose. The aim of this study is to explore pathological mechanisms of bone fragility in type 2 diabetes mellitus (T2DM) patients. Methods. Identifying common genes for T2DM and osteoporosis by taking the intersection is shared by the Comparative Toxicogenomics Database (CTD), DISEASES, and GeneCards databases. The differentially expressed genes (DEGs) and the differentially expressed miRNAs (DEMs) were identified by analyzing the Gene Expression Omnibus (GEO) datasets (GSE35958, GSE43950, and GSE70318). FunRich and miRNet were applied to predict potential upstream transcription factors and downstream target genes of candidate DEMs, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential mechanisms using Metascape. Eventually, a miRNA-gene network was constructed by Cytoscape software. Results. 271 common targets and 35 common DEGs between T2DM and osteoporosis were screened out in the above databases, and a total of ten DEMs were obtained in the GSE70318. SP1 was predicted to potentially regulate most of the DEMs. Enrichment analysis showed the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play an important role in diabetic skeletal fragility. Two genes (NAMPT and IGFBP5) were considered as key genes involving in the development of diabetic osteoporosis. Through the construction of the miRNA-gene network, most of the hub genes were found to be potentially modulated by miR-96-5p and miR-7-5p. Conclusion. The study uncovered several important genes, miRNAs, and pathological mechanisms involved in diabetic skeletal fragility, among which the PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications may play important roles.
Background
The exact pathogenesis of steroid-induced osteonecrosis of the femoral head (SIONFH) is not yet clearly understood. Studies suggest programmed cell death as one of the potential pathological mechanisms. The purpose for this study was to investigate the molecular mechanisms associated with mitophagy in SIONFH. To ascertain the potentially proteins and signaling pathways involved during bone repair.
Methods
Femur bones from patients with SIONFH were collected and divided into Healthy, Necrotic and Sclerotic zones for proteomic testing. We performed the Kyoto Encyclopedia of Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analysis. Cellular experiments were used to verify the changes in mitochondrial function during osteoclast formation. Furthermore, specific target proteins were analyzed by protein-protein interaction (PPI) networks and venn diagrams.
Results
A total of 575 protein targets were selected for enrichment analysis. The results revealed that the bone repair process mostly involved osteoclast differentiation, FOXO signaling pathway, mTOR signaling pathway, autophagy, and mitochondrial function. Cellular experiments verified that mitochondrial function changed during osteoclast differentiation and was closely related to mitophagy. Finally, PPI network and Venn diagram were used to identify core target proteins with important roles, such as mTOR and SOD1.
Conclusion
This study will provide new insights about the proteins and relevant pathways involved in SIONFH. Bone repair process is closely related to mitophagy.
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