Identification and validation of iron metabolism genes in osteoporosis.

BACKGROUND: Osteoporosis is the most common metabolic bone disease in humans. Exploring the expression difference of iron metabolism-related genes in osteoporosis can provide a new target for diagnosis and treatment. METHODS: First, we used online databases to identify differentially expressed genes (DEGs) related to iron metabolism in patients with osteoporosis. The differential genes were comprehensively analyzed by bioinformatics method (GO, KEGG, GSEA, immune infiltration analysis, PPI). The expression levels of hub genes and important signaling pathways were verified by qRT-PCR and Western blotting. RESULTS: A total of 23 iron metabolism-related genes with significant differences were identified, which were enriched in "regulation of protein dephosphorylation" and "negative regulation of protein dephosphorylation". The GSEA results, heme metabolism and Myc targets v1 were among the top two pathways, both upregulated. The immune infiltration analysis revealed that the expressions of genes such as ABCA5, D2HGDH, GNAI2, and CTSW were correlated with the infiltration degree of significantly different cells. The PPI network contained 12 differentially expressed iron metabolism-related genes. Additionally, YWHAE, TGFB1, PPP1R15A, TOP2A, and CALR were mined as hub genes using the Cytoscape software. qRT PCR showed that the expression of TGF-ß1, YWHAE, TOP2A and CALR increased. We also verified the expression of related proteins and genes in the oxidative stress signaling pathway by qRT PCR and Western blotting. The results showed that Mob1, YAP and TAZ molecules were highly expressed at the gene and protein levels. CONCLUSIONS: These differentially expressed iron metabolism-related genes could provide new potential targets for the diagnosis and treatment of osteoporosis.

MicroRNA-194-3p inhibits the metastatic biological behaviors of spinal osteosarcoma cells by the repression of matrix metallopeptidase 9.

Osteosarcoma is the most common primary malignant bone tumor, but only 3%-5% of cases occur in the spine. Spinal osteosarcoma presents a significant challenge, and most patients die in spite of aggressive surgery. MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression. The aim of this study was to investigate the role of miR-194-3p and to identify its potential mechanism in spinal osteosarcoma. Here, spinal osteosarcoma tissues showed down-regulated expression of miR-194-3p compared to adjacent non-tumorous tissues. The level of miR-194-3p was negatively correlated with metastasis in patients with spinal osteosarcoma. MiR-194-3p over-expression in spinal osteosarcoma cells significantly inhibited cell migration and invasion in vitro. Furthermore, mechanistic analyses showed that MMP-9 (matrix metallopeptidase 9) is a direct target of miR-194-3p, and the ectopic expression of miR-194-3p inhibits MMP-9 expression by directly binding to the 3'-untranslated region (3'-UTR) of the MMP-9 gene. In summary, our results demonstrate that miR-194-3p suppresses migration and invasion of spinal osteosarcoma cells by targeting MMP-9, indicating miR-194-3p may serve as a promising novel target for spinal osteosarcoma therapy.

Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of patients with osteosarcoma.

MicroRNA-183 (miR-183) has been demonstrated to be a tumor suppressor miRNA in inhibition of migration and invasion of osteosarcoma by targeting an oncogene Ezrin. The aim of the present study was to determine the correlation of combined miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis in patients with osteosarcomas. Expressions of MiR-183 and Ezrin mRNA were both examined using quantitative real-time reverse transcriptase-polymerase chain reaction analysis in 68 specimens from patients with osteosarcomas. MiR-183 and Ezrin mRNA expression levels were, respectively, lower and higher in osteosarcoma tissues than those in noncancerous bone tissues significantly (both P < 0.001). Notably, the downregulation of miR-183 was negatively correlated with the upregulation of Ezrin mRNA in osteosarcoma tissues (r = -0.66, P = 0.01). In addition, the combined miR-183 downregulation and Ezrin upregulation (miR-183-low/Ezrin-high) was significantly associated with high tumor grade (P = 0.02), poor response to chemotherapy (P = 0.01), positive metastasis (P = 0.006) and recurrence (P = 0.008). Moreover, miR-183/Ezrin expression and the status of metastasis were both found to be independent prognostic factors for overall survival (P = 0.02 and 0.01, respectively) and disease-free survival (both P = 0.02). Our findings showed that the aberrant expression of miR-183 and its target gene Ezrin may play a crucial role in the development and progression of human osteosarcoma. More interestingly, the dysregulation of miR-183/Ezrin axis may be related to the prediction of aggressiveness and poor prognosis for patients with this lethal disease.

[Comparison between surgical and conservative treatment for postoperative lumbar discitis].

OBJECTIVE: To compare therapeutic effects between surgical and conservative treatment for postoperative lumbar discitis. METHODS: From January 2004 to January 2009, 41 patients (17 males and 24 females ranging the age from 37 to 68 years with an average of 53.6 years) with postoperative lumbar discitis were retrospectively studied and divided into two groups. There were 19 patients in operation group, 22 patients in conservative group. Clinical data and features,image data, laboratory examinations, antibiotics utilization, hospital stays and sequelae were recorded and analyzed. Visual analogue scales system (VAS) and Oswestry disability index (ODI) were applied to evaluate therapeutic effects. RESULTS: All patients were followed up over 2 years. Imaging revealed good bone fusion and no occurrence of discitis. VAS score and ODI at 1 month, 1 year and 2 years were significantly improved after treatment (P < 0.01). While VAS and ODI in operation group at 1 month were improved more than that of conservative group (P < 0.01), and there was no significant difference between two groups at 1 year and 2 years (P > 0.01). CONCLUSION: Surgical and conservative treatment for postoperative lumbar discitis is effective. Surgical treatment is superior to conservative treatment in a short time, while conservative treatment can achieve long-term satisfactory curative effects.