Eunyi Jeon

Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration

Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

Administration of growth factors for bone regeneration

Growth factors (GFs) such as BMPs, FGFs, VEGFs and IGFs have significant impacts on osteoblast behavior, and thus have been widely utilized for bone tissue regeneration. Recently, securing biological stability for a sustainable and controllable release to the target tissue has been a challenge to practical applications. This challenge has been addressed to some degree with the development of appropriate carrier materials and delivery systems. This review highlights the importance and roles of those GFs, as well as their proper administration for targeting bone regeneration. Additionally, the in vitro and in vivo performance of those GFs with or without the use of carrier systems in the repair and regeneration of bone tissue is systematically addressed. Moreover, some recent advances in the utility of the GFs, such as using fusion technology, are also reviewed.

Engineering and application of collagen‐binding fibroblast growth factor 2 for sustained release

The sustained release of growth factors plays a critical role in therapeutic applications because of the instability of these factors in the body. Here, we designed a fibroblast growth factor 2 (FGF2) fused with a collagen-binding domain (rhCBD-FGF2) for collagen-based sustained release of FGF2.The release profile of rhCBD-FGF2 showed sustained release from collagen matrices. Further, rhCBD-FGF2 also stimulated adhesion of the MC3T3-E1 cells to the collagen matrices. In addition, rhCBD-FGF2 increased the cell proliferation activity at 3 and 5 days in the MC3T3-E1 cells attached to the collagen matrices compared to that in the control. Further, rhCBD-FGF2 significantly induced the osteogenic differentiation of MC3T3-E1 cells on collagen matrices by up-regulating the alkaline phosphatase activity at 7 days. These osteogenic differentiation activities were confirmed in gene expression of MC3T3-E1 cell. Taken together, rhCBD-FGF2 could specifically bind with collagen matrices, which indicates important advancements in bone tissue engineering.

Investigating the Role of FGF18 in the Cultivation and Osteogenic Differentiation of Mesenchymal Stem Cells

Fibroblast growth factor18 (FGF18) belongs to the FGF family and is a pleiotropic protein that stimulates proliferation in several tissues. Bone marrow mesenchymal stem cells (BMSCs) participate in the normal replacement of damaged cells and in disease healing processes within bone and the haematopoietic system. In this study, we constructed FGF18 and investigated its effects on rat BMSCs (rBMSCs). The proliferative effects of FGF18 on rBMSCs were examined using an MTS assay. To validate the osteogenic differentiation effects of FGF18, ALP and mineralization activity were examined as well as osteogenic differentiation-related gene levels. FGF18 significantly enhanced rBMSCs proliferation (p<0.001) and induced the osteogenic differentiation by elevating ALP and mineralization activity of rBMSCs (p<0.001). Furthermore, these osteogenic differentiation effects of FGF18 were confirmed via increasing the mRNA levels of collagen type I (Col I), bone morphogenetic protein 4 (BMP4), and Runt-related transcription factor 2 (Runx2) at 3 and 7 days. These results suggest that FGF18 could be used to improve bone repair and regeneration.

RETRACTED: Identification and Analysis of Differentially Expressed Genes in Mountain Cultivated Ginseng and Mountain Wild Ginseng

Ginseng is one of the most widely used herbal medicines in the world. Wild ginseng is thought to be more effective than cultivated ginseng in chemoprevention; however, little has been reported on the differences between wild and cultivated ginseng. In the present study we used suppressive subtractive hybridization to identify wild ginseng-specific genes. One of the clones isolated in this screen was the NRT2 gene (designated pNRT2), a high-affinity nitrate transporter. Real-time reverse transcription-polymerase chain reaction results showed that pNRT2 expression was significantly upregulated in wild ginseng compared with cultivated ginseng. However, pNRT2 mRNA levels were similar between mountain cultivated ginseng and mountain wild ginseng. Nitrate is an important nitrogen source for plant growth, and its soil levels can vary in wild environments; thus it is conceivable that pNRT2 expression is upregulated in wild ginseng and may be an important marker of wild ginseng.

Emerging role of vitamin D in colorectal cancer

Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D(3) reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer.

Construction and expression of a recombinant fibronectinIII10 protein for integrin-mediated cell adhesion

Specific sequences of cell-adhesive peptide/proteins are often required for the bio-inert synthetic polymers to improve cell adhesion. We have developed a recombinant fibronectin fragment (FNIII10), the central cell-binding domain containing RGD motif, to endow biomaterial surfaces with abilities to promote an integrin-mediated cell adhesion. Immobilized FNIII10 stimulated adhesion of MC3TC-E1 cells in an integrin-dependent manner.

Characterization and optimization of vascular endothelial growth factor165 (rhVEGF165) expression in Escherichia coli

Vascular endothelial growth factors(165) (VEGF(165)) is the most potent and widely used pro-angiogenic factor. Here we determined optimal culture condition of recombinant human VEGF(165) (rhVEGF(165)) in Escherichia coli (E. coli). rhVEGF(165) expression was the highest in 0.25% of L-arabinose induction concentration, at 20 °C induction temperature, and for 5 h induction time under the control of araBAD promoter using pBADHisA vector. In biological activity test, rhVEGF(165) significantly increased the proliferative activity of CPAE cells (p<0.001) and upregulated the expressions of endothelial cell growth-related genes, such as platelet endothelial cell adhesion molecule (PECAM-1), endothelial-specific receptor tyrosine kinase (TEK), kinase insert domain protein receptor (KDR), and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) in calf pulmonary artery endothelial (CPAE) cells.

Expression and purification recombinant human dentin sialoprotein in Escherichia coli and its effects on human dental pulp cells

Dentin sialoprotein (DSP) is cleaved from dentin sialophosphoprotein (DSPP) and most abundant dentinal non-collagenous proteins in dentin. DSP is believed to participate in differentiation and mineralization of cells. In this study, we first constructed recombinant human DSP (rhDSP) in Escherichia coli (E. coli) and investigated its odontoblastic differentiation effects on human dental pulp cells (hDPCs). Cell adhesion activity was measured by crystal violet assay and cell proliferation activity was measured by MTT assay. To assess mineralization activity of rhDSP, Alizarin Red S staining was performed. In addition, the mRNA levels of collagen type І (Col І), alkaline phosphatase (ALP), and osteocalcin (OCN) were measured due to their use as mineralization markers for odontoblast-/osteoblast-like differentiation of hDPCs. The obtained rhDSP in E. coli was approximately identified by SDS-PAGE and Western blot. Initially, rhDSP significantly enhanced hDPCs adhesion activity and proliferation (p<0.05). In Alizarin Red S staining, stained hDPCs increased in a time-dependent manner. This odontoblastic differentiation activity was also verified through mRNA levels of odontoblast-related markers. Here, we first demonstrated that rhDSP may be an important regulatory ECM in determining the hDPCs fate including cell adhesion, proliferation, and odontoblastic differentiation activity. These findings indicate that rhDSP can induce growth and differentiation on hDPCs, leading to improve tooth repair and regeneration.

Protein Engineering of a Fibroblast Growth Factor 2 Protein for Targeting to Bone Mineral Hydroxyapatite

The engineering of a novel FGF2 fused with highly conserved bone mineral-binding domain of osteocalcin (OC) for targeting to bone mineral hydroxyapatite (HA) exhibited much stronger HA-binding affinity than native FGF2. FGF2-OC also showed a significant increase of mitogenic activity and cellular differentiation of osteoblastic cells compared with native FGF2.