Bone formation occurs by two distinct mechanisms, namely, periosteal ossification and endochondral ossification. In both mechanisms, osteoblasts play an important role in the secretion and mineralization of bone-specific extracellular matrix. Differentiation and maturation of osteoblasts is a prerequisite to bone formation and is regulated by many factors. Recent experiments have shown that transcription factors play an important role in regulating osteoblast differentiation, proliferation, and function. Osteogenesis related transcription factors are the central targets and key mediators of the function of growth factors, such as cytokines. Transcription factors play a key role in the transformation of mesenchymal progenitor cells into functional osteoblasts. These transcription factors are closely linked with each other and in conjunction with bone-related signaling pathways form a complex network that regulates osteoblast differentiation and bone formation. In this paper, we discuss the structure of T-cell factor/lymphoid enhancer factor (TCF/LEF) and its role in embryonic skeletal development and the crosstalk with related signaling pathways and factors.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with highly heterogeneous clinical symptoms and severity. There is complex pathogenesis of SLE, one of which is IFNs overproduction and downstream IFN-stimulated genes (ISGs) upregulation. Identifying the key ISGs differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients with SLE and healthy people could help to further understand the role of the IFN pathway in SLE and discover potential diagnostic biomarkers.The differentially expressed ISGs (DEISG) in PBMCs of SLE patients and healthy persons were screened from two datasets of the Gene Expression Omnibus (GEO) database. A total of 67 DEISGs, including 6 long noncoding RNAs (lncRNAs) and 61 messenger RNAs (mRNAs) were identified by the “DESeq2” R package. According to Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, those DEISGs were mainly concentrated in the response to virus and immune system processes. Protein-protein interaction (PPI) network showed that most of these DEISGs could interact strongly with each other. Then, IFIT1, RSAD2, IFIT3, USP18, ISG15, OASL, MX1, OAS2, OAS3, and IFI44 were considered to be hub ISGs in SLE by “MCODE” and “Cytohubba” plugins of Cytoscape, Moreover, the results of expression correlation suggested that 3 lncRNAs (NRIR, FAM225A, and LY6E-DT) were closely related to the IFN pathway.The lncRNA NRIR and mRNAs (RSAD2, USP18, IFI44, and ISG15) were selected as candidate ISGs for verification. RT-qPCR results showed that PBMCs from SLE patients had substantially higher expression levels of 5 ISGs compared to healthy controls (HCs). Additionally, statistical analyses revealed that the expression levels of these ISGs were strongly associated to various clinical symptoms, including thrombocytopenia and facial erythema, as well as laboratory indications, including the white blood cell (WBC) count and levels of autoantibodies. The Receiver Operating Characteristic (ROC) curve demonstrated that the IFI44, USP18, RSAD2, and IFN score had good diagnostic capabilities of SLE.According to our study, SLE was associated with ISGs including NRIR, RSAD2, USP18, IFI44, and ISG15, which may contribute to the future diagnosis and new personalized targeted therapies.

Oral squamous cell carcinoma ( OSCC ) is one of the most common head and neck malignancies. Advanced stages of the disease are associated with poor survival, highlighting a need for new treatment modalities. We previously showed that the proinflammatory cytokine interleukin‐18 ( IL ‐18) has a tumor suppressive role in OSCC . Here, we investigated the effects of IL ‐18 on proliferation, migration, and invasion of OSCC cells ex vivo and in vitro , and in nude mouse xenografts. We report that expression of tankyrase 2 ( TNKS 2), β‐catenin, and N‐cadherin was higher in tumor cells than in normal mucosae, whereas the expression of IL ‐18 and E‐cadherin was higher in normal than in tumor tissues. Elevated expression of IL ‐18 ( P < 0.01) and E‐cadherin ( P = 0.034) was associated with tumor differentiation, whereas expression of TNKS 2 ( P < 0.01), β‐catenin ( P = 0.012), and N‐cadherin ( P < 0.01) was associated with tumor de‐differentiation. Furthermore, compared with the vector control, IL ‐18 overexpression promoted tumor cell migration and invasion ( P < 0.01), but inhibited growth of tumor cell xenografts ( P < 0.05). At the protein level, expression levels of IL ‐18 ( P < 0.01), TNKS 2 ( P = 0.045), β‐catenin ( P = 0.028), and N‐cadherin ( P = 0.068) were upregulated in tumor cells after IL ‐18 overexpression compared with those of the vector control mice, whereas expression levels of E‐cadherin ( P = 0.045) were decreased. In conclusion, our data suggest that IL ‐18 overexpression induces oral SCC cell invasion and metastasis by promoting the tumor cell epithelial–mesenchymal transition via the Wnt/β‐catenin signaling pathway.

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