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Objective: To explore the key genes and potential therapeutic drugs for osteoarthritis (OA) by bioinformatics.Method: The microarray data GSE55235 was downloaded from the data platform of gene expression omnibus (GEO) and the differentially expressed genes were screened by R language software (3.5.0).Then,the differentially expressed genes were subjected to gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis with David online database.The protein-protein interaction was analyzed by String 10.5 online database and visual editing was analyzed by Cytoscape v3.6.1 software.Subnetwork module analysis was utilized by MCODE plugin to screen the core genes in the process of OA.Finally,small molecule drugs with potential treatment for OA were analyzed by connectivity map (CMap) database.Result: A total of 556 differentially expressed genes were screened,among which 252 were up-regulated and 304 were down-regulated.These genes were mainly involved in extracellular matrix (ECM) organization,inflammatory response,cell adhesion,immune response,collagen binding,etc.The analysis of KEGG pathway showed that differential genes were mainly involved in ECM-receptor interaction,phosphatidylinositol 3 kinase-protein kinase B (PI3K/Akt) signaling pathway and osteoclast differentiation.Some genes,such as interleukin-6(IL-6),JUN,vascular endothelial growth factor α(VEGFA),FOS,MYC and early growth response gene-1(EGR-1),activating transcription factor-3(ATF-3),playing critical role in the process of OA were identified by protein-protein interaction.Some potential small molecular drugs for the treatment of OA have also been screened,such as lycorine and anisomycin.Conclusion: The selected key genes may be targets for the diagnosis of OA or potential targets for the treatment of OA,and the selected small molecular drugs can be developed as the key drugs for the treatment of OA.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the feasibility of prevention and treatment of early scar through observing the effect of feeding immunosuppressive drug cyclophosphamide on rabbit ears hypertrophic scar tissue in early stage.</p><p><b>METHODS</b>Thirty-two Rabbit ears were used to establish animal models for hypertrophic scar and randomly divided into four groups: group of distilled water (A), group of cyclophosphamide 5 mg x kg(-1) x d(-1) (B), group of 10 mg x kg(-1) x d(-1) (C), group of 30 mg x kg(-1) x d(-1) (D). Before animal models were built and after administration for 14 days, 28 days, leukocytes and lymphocytes were detected. After 28 days, specimens were harvested and underwent HE staining and VG staining in order to assess HI, NA, AA value changes. The data (HI, NA, AA) from each group were compared by analysis of variance, and the variance for the rank sum test when missing.</p><p><b>RESULTS</b>On the 14th day, the number of leukocytes in group A, B, C, D were (8.62 +/- 0.58) x 10(9)/L, (4.48 +/- 0.41) x 10(9)/L, (2.7 +/- 0.26) x 10(9)/L, (1.33 +/- 0.27) x 10(9)/L; the number of lymphocytes in group A, B, C, D were (3.11 +/- 0.21) x 10(9)/L, (1.67 +/- 0.16) x 10(9)/L, (0.42 +/- 0.10) x 10(9)/L, (0.40 +/- 0.09) x 10(9)/L. On the 28th day, the number of leukocytes in group A, B, C, D was (8.63 +/- 0.53) x 10(9)/L, (5.10 +/- 0.27) x 10(9)/L, (3.10 +/- 0.26) x 10(9)/L, (1.98 +/- 0.20) x 10(9)/L; the number of lymphocytes A, B, C, D was (3.06 +/- 0.16) x 10(9)/L, (2.08 +/- 0.14) x 10(9)/L, (0.96 +/- 0.19) x 10(9)/L, (0.14 +/- 0.07) x 10(9)/L. On the 14th day and 28th day, the number of leukocytes and lymphocytes in experimental groups was reduced, showing a negative relation with cyclophosphamide dose (P < 0.05). The HI in group of A, B, C, D was 3.02 +/- 0.24, 2.59 +/- 0.43, 2.06 +/- 0.19, 1.63 +/- 0.11; the AA was 40.49 +/- 2. 07, 35.29 +/- 1.99, 28.36 +/- 1.87, 24.99 +/- 1.82; the NA was 4570.5 +/- 259.3, 4222.5 +/- 199.6, 3540.3 +/- 170.3, 3341.4 +/- 228.8. The difference in HI, AA, NA between control group and any of the experimental groups was statistically significant (P < 0.01). Each group, with the dose increased, except NA content of group C and D, the HI, AA, NA was more smaller, negative correlation, the difference was statistically significant (P < 0.05).</p><p><b>CONCLUSIONS</b>Feeding cyclophosphamide can inhibit leukocytes and lymphocytes number, so as to inhibit the proliferative activity of hypertrophic scar. It has significant effect on prevention of hypertrophic scar on rabbit ears in early stage.</p>