Background Osteosarcoma is the most common bone tumor that occurs in children. Methods To identify co-expression modules and pathways correlated with osteosarcoma and its clinical characteristics, we performed weighted gene co-expression network analysis (WGCNA) on RNA-seq data of osteosarcoma with 52 samples. Then we performed pathway enrichment analysis on genes from significant modules. Results A total of 5471 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that a module involved in microtubule bundle formation, drug metabolism-cytochrome P450, and IL-17 signaling pathway was negatively correlated with osteosarcoma and positively correlated with metastasis; a module involved in DNA replication was positively correlated with osteosarcoma; a module involved in cell junction was positively correlated with metastasis; and a module involved in heparin binding negatively correlated with osteosarcoma. Moreover, expression levels in four of the top ten differentially expressed genes were validated in another independent dataset. Conclusions Our analysis might provide insight for molecular mechanisms of osteosarcoma. Electronic supplementary material The online version of this article (10.1186/s12957-019-1587-7) contains supplementary material, which is available to authorized users.

Background/Aims: Renal tubular epithelial-mesenchymal transition (EMT) is regarded as an important factor leading to renal interstitial fibrosis. Erythropoietin (EPO) has been reported to attenuate renal fibrosis. The mechanism underlying this protective effect of EPO remains unclear. In this study, we aim to identify possible mechanisms of the EPO renoprotective effect. Methods: Hypoxia was induced in vitro by incubating human proximal tubular epithelial cell line HK-2 cells in 1% O₂ and 5% CO₂. Western blotting and reverse transcription polymerase chain reaction analyses were used to evaluate the expression of epithelial and mesenchymal markers in the cell samples. The expression of miR-200b in the HK-2 cells under hypoxia or treatment with EPO was examined. Results: EPO represses hypoxia-induced EMT by upregulating miR-200b in HK-2 cells. Overexpression of miR-200b represses the effect of ETS proto-oncogene 1 (Ets-1)-induced EMT in HK-2 cells. Conclusion: miR-200 mediates the protective effects of EPO on EMT in hypoxic HK-2 cells. EPO attenuated hypoxia-induced EMT by increasing miR-200 expression via the repression of Ets-1.

BackgroundEndothelial-to-mesenchymal transition (EndoMT) is a crucial event during kidney interstitial fibrosis and it is believed to be inhibited by netrin-1. Our aim was to determine the influence of netrin-1 on renal EndoMT in chronic kidney disease by studying its effect in 5/6 nephrectomized (Nx) rats.MethodsMale Sprague–Dawley rats were divided into three groups (10 rats/group): sham-operated rats treated with control adenovirus; 5/6 Nx rats treated with control adenovirus; and 5/6 Nx rats treated with recombinant adenovirus expressing the netrin-1 gene (Ad-netrin-1). Rats were sacrificed 13 weeks after surgery. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels were measured regularly after surgery. After the rats were sacrificed, pathological changes in renal tissues were analyzed histologically. Immunofluorescence was performed to evaluate the co-expression of CD31 and α-SMA. CD31, α-SMA and Snail mRNA were detected by RT-PCR. Protein expression was detected by western blot.ResultsRenal function and histopathological damage were significantly improved in Ad-netrin-1-treated 5/6 Nx rats. In the sham and control-treated 5/6 Nx rats, the percentage of CD31+/α-SMA+ cells increased, which indicated EndoMT. However, the percentage of CD31+/α-SMA+ cells were reduced in the netrin-1-treated 5/6 Nx rats, which indicates netrin-1-induced blocking of EndoMT.ConclusionFrom the results, it seems that netrin-1 attenuates the progression of renal dysfunction by inhibiting EndoMT in 5/6 Nx rats. Netrin-1 can therefore be considered as a potential therapeutic agent for the treatment of renal fibrosis.

The aim of the present study was to identify the functional role of galectin-3 (Gal-3) in lipopolysaccharide (LPS)-induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal-3 in ATDC5 cells. In addition, repression of Gal-3 obviously impeded LPS-stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)-13 and MMP-3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal-3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl-2 and a decrease in the expression of proapoptotic protein Bax and caspase-3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR-γ with the antagonist GW9662 effectively abolished Gal-3 inhibition-mediated anti-inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal-3 prevents the NF-κB signaling pathway. Taken together, these findings indicated that the absence of Gal-3 exerted chondroprotective properties dependent on TLR4 and PPAR-γ-mediated NF-κB signaling, indicating that Gal-3 functions as a protector in the development and progression of osteoarthritis.

Osteosarcoma (OS) is the most common primary bone malignancy. It predominantly occurs in adolescents, but can develop at any age. The age at diagnosis is a prognostic factor of OS, but the molecular basis of this remains unknown. The current study aimed to identify age-induced differentially expressed genes (DEGs) and potential molecular mechanisms that contribute to the different outcomes of patients with OS. Microarray data (GSE39058 and GSE39040) obtained from the Gene Expression Omnibus database and used to analyze age-induced DEGs to reveal molecular mechanism of OS among different age groups (<20 and >20 years old). Differentially expressed mRNAs (DEMs) were divided into up and downregulated DEMs (according to the expression fold change), then Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Furthermore, the interactions among proteins encoded by DEMs were integrated with prediction for microRNA-mRNA interactions to construct a regulatory network. The key subnetwork was extracted and Kaplan-Meier survival analysis for a key microRNA was performed. DEMs within the subnetwork were predominantly involved in ‘ubiquitin protein ligase binding’, ‘response to growth factor’, ‘regulation of type I interferon production’, ‘response to decreased oxygen levels’, ‘voltage-gated potassium channel complex’, ‘synapse part’, ‘regulation of stem cell proliferation’. In summary, integrated bioinformatics was applied to analyze the potential molecular mechanisms leading to different outcomes of patients with OS among different age groups. The hub genes within the key subnetwork may have crucial roles in the different outcomes associated with age and require further analysis.