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The Wnt/β-catenin signaling and TGFβ signaling pathways play a key role in osteoblast differentiation. The miRNAs play important roles in regulating gene expression at the post-transcriptional level through fine-tuning of protein-encoding gene expression. However, involvement of miRNAs is not established for Wnt3a and TGFβ signaling pathways in osteoblast differentiation. Here, we examined the role of miRNAs expressed differentially after Wnt3a expression during osteoblast differentiation. Over-expression of the Wnt3a gene increased ALP transcription, but decreased Col1, Runx2, and OCN transcription in osteoblastic MC3T3-E1 cells. Expression profiling and quantitative PCR for miRNAs showed that miR-140-3p decreased in Wnt3a-over-expressing osteoblastic cells. Wnt3a over-expression increased TGFβ3 expression, whereas transfection of the miR-140-3p mimic into MC3T3-E1 cells significantly inhibited TGFβ3 expression. Luciferase assay for the TGFβ3 transcript showed that TGFβ3 was a direct target of miR-140-3p. miR-140-3p mimic transfection resulted in significantly increased OCN transcription, but did not affect ALP, Col1, and Runx2 transcription in MC3T3-E1 cells. rTGFβ3 treatment decreased OCN transcription in MC3T3-E1 cells. These results suggest that the miR-140-3p is involved in osteoblast differentiation as a critical regulatory factor between Wnt3a and TGFβ3 signaling pathways.

Insulin-like growth factors, IGF-I and IGF-II, play important roles in development and myelination in the CNS, but little is known about the response of IGF after demyelination. The present study investigated the expression of IGF and their cognitive receptors in the process of remyelination following ethidium bromide (EBr)-induced demyelination in the adult mouse spinal cord. The present results, in a quantitative real-time PCR, showed significant increases in the levels of the mRNA for both IGF-I and IGF-II during both the demyelination and remyelination stages. The levels of IGF-I receptor (IGF-IR) mRNA increased from 10 days to 4 weeks after the EBr injection. The levels of IGF-II receptor (IGF-IIR) mRNA decreased for 6 days and then increased 10 days after the EBr injection. In situ hybridization studies showed the cells expressing IGF-I mRNA to be mainly macrophage-like cells, while those expressing IGF-II mRNA were predominantly Schwann cell-like cells invading the demyelinating lesion. The immunoreactivity for the IGF-IR and IGF-IIR increased in various kinds of cells within and around the demyelinating lesions from 6 days to 4 weeks after the EBr injection. These results suggest that locally produced IGF could partly be involved in some mechanisms underlying remyelination processes following the EBr-induced demyelination in the mouse spinal cord.

Stromal cells in the tumor microenvironment (TME) can regulate the progression of numerous types of cancer; however, the bone invasion of oral squamous cell carcinoma (OSCC) has been poorly investigated. In the present study, the effect of verrucous SCC-associated stromal cells (VSCC-SCs), SCC-associated stromal cells (SCC-SCs) and human dermal fibroblasts on bone resorption and the activation of HSC-3 osteoclasts in vivo were examined by hematoxylin and eosin, AE1/3 (pan-cytokeratin) and tartrate-resistant acid phosphatase staining. In addition, the expression levels of matrix metalloproteinase (MMP)9, membrane-type 1 MMP (MT1-MMP), Snail, receptor activator of NF-κB ligand (RANKL) and parathyroid hormone-related peptide (PTHrP) in the bone invasion regions of HSC-3 cells were examined by immunohistochemistry. The results suggested that both SCC-SCs and VSCC-SCs promoted bone resorption, the activation of osteoclasts, and the expression levels of MMP9, MT1-MMP, Snail, RANKL and PTHrP. However, SCC-SCs had a more prominent effect compared with VSCC-SCs. Finally, microarray data were used to predict potential genes underlying the differential effects of VSCC-SCs and SCC-SCs on bone invasion in OSCC. The results revealed that IL1B, ICAM1, FOS, CXCL12, INS and NGF may underlie these differential effects. In conclusion, both VSCC-SCs and SCC-SCs may promote bone invasion in OSCC by enhancing the expression levels of RANKL in cancer and stromal cells mediated by PTHrP; however, SCC-SCs had a more prominent effect. These findings may represent a potential regulatory mechanism underlying the bone invasion of OSCC.

The present study investigated how glial progenitor cells participated in the process of remyelination following ethidium bromide (EBr)-induced demyelination in the adult mouse spinal cord. In situ hybridization techniques for detecting mRNA for platelet-derived growth factor alpha receptor (PDGFalphaR) and proteolipid protein (PLP) were employed to identify glial progenitor cells and mature oligodendrocytes, respectively. During the demyelination stage and early stage of remyelination, large cells strongly expressing PDGFalphaR mRNA were observed in the border of the demyelinating lesion, and with immunohistochemistry they exhibited positive labeling of the astrocytic marker glial fibrillary acidic protein (GFAP). Other glial progenitor cells expressing PDGFalphaR mRNA proliferated around the lesion during the demyelination stage. During the remyelination stage, some PDGFalphaR mRNA-positive cells partly expressed mRNA for PLP in the periphery of the demyelinating lesion. These results suggest that PDGFalphaR mRNA-positive glial progenitor cells may give rise to both astrocytes and oligodendrocytes, which participate in remyelination following demyelination.

Tissue Engineering (TE) is an interdisciplinary field that encompasses materials science in combination with biological and engineering sciences. In recent years, an increase in the demand for therapeutic strategies for improving quality of life has necessitated innovative approaches to designing intelligent biomaterials aimed at the regeneration of tissues and organs. Polymeric porous scaffolds play a critical role in TE strategies for providing a favorable environment for tissue restoration and establishing the interaction of the biomaterial with cells and inducing substances. This article reviewed the various polymeric scaffold materials and their production techniques, as well as the basic elements and principles of TE. Several interesting strategies in eight main TE application areas of epithelial, bone, uterine, vascular, nerve, cartilaginous, cardiac, and urinary tissue were included with the aim of learning about current approaches in TE. Different polymer-based medical devices approved for use in clinical trials and a wide variety of polymeric biomaterials are currently available as commercial products. However, there still are obstacles that limit the clinical translation of TE implants for use wide in humans, and much research work is still needed in the field of regenerative medicine.

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