• BMB Reports
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• 제50권2호
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• pp.58-59
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• 2017

The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

• 구강회복응용과학지
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• 제23권2호
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• pp.179-186
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• 2007

The decrease of masticatory function caused by tooth loss leads to a decrease of cerebral blood flow volume resulting in impairment of cognitive function and learning memory disorder. However, the reduced mastication-mediated morphological alteration in the central nervous system (CNS) responsible for senile deficit of cognition, learning and memory has not been well documented. In this study, the effect of the loss of the molar teeth (molarless condition) on the hippocampal expression of glial fibrillary acidic protein (GFAP) protein was studied by immunohistochemical techniques. The results were as follows : 1. The molarless mice showed a lower density of pyramidal cells in the cornu ammonis 1 (CA1) and dentate gyrus (DG) region of the hippocampus than control mice. 2. Immunohistochemical analysis showed that the molarless condition enhanced the time-dependent increase in the cell density and hypertrophy of GFAP immunoreactivity in the CA1 region of the hippocampus. The molarless condition enhanced an time-dependent decrease in the number of neurons in the hippocampal formation and the time-dependent increase in the number and hypertrophy of GFAP-labeled cells in the same region. The data suggest a possible link between reduced mastication and histological changes in hippocampal formation that may be one risk factor for senile impairment of cognitive function and spatial learning memory.

• Journal of Microbiology and Biotechnology
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• 제16권4호
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• pp.531-537
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• 2006

Lactic acid-producing bacteria (LABs) are known to have various beneficial properties for health. However, they are generally considered to have an adverse effect on teeth, since they produce acid. Nonetheless, milk and cheese containing specific LAB strains were recently found to have an inhibitory effect on dental caries in children, with an inhibitory activity towards the growth of Streptococcus mutans suggested as the responsible mechanism. Accordingly, the current study selected a probiotic candidate for oral health and studied its inhibitory mechanism against dental caries. Twenty-two LAB species belonging to eleven genuses were screened for promoting bone nodule formation using direct microscopic examination. Only one isolate, Weissella kimchii strain PL9001, increased the bone nodule formation significantly. The addition of W. kimchii strain PL9001 to bone cells prepared from mouse calvaria increased the bone nodule formation, calcium accumulation, and activity of alkaline phosphatase (the osteoblastic marker). Moreover, W. kimchii strain PL9001 inhibited the invasion of Streptococcus mutans into bone cells, and an organic extract of the culture supernatant of W. kimchii strain PL9001 inhibited the growth of Strep. mutans. Therefore, the results suggest that W. kimchii strain PL9001 can be used as a preventive measure against dental caries. This is the first time that a LAB has been shown to promote bone nodule formation and prevent the invasion of Strep. mutans into bone cells.

• Archives of Plastic Surgery
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• 제38권4호
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• pp.339-344
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• 2011

Purpose: The goal of cancer surgery is complete removal of cancer tissue and prevention of recurrence. Surgeons can change the surgical instruments after total resection of the cancer mass. The purpose of this procedure is to prevent dissemination of the cancer cells attached to the surgical instruments. Authors hypothesize the possibility of local recurrence caused by the cancer cells attached to the surgical instruments in the skin cancer cases. Methods: Skin cancers were induced by using DMBA-TPA two-stage carcinogenesis model in 10 of Balb/c mice. In 2-weeks, skin cancer was developed in all 10 mice. cancer cell attached surgical instruments were made by pinching the removed cancer tissue using Adson tissue forcep 10, 20, 30 times each. To count number of cancer cells in each forcep with different number of pinching was done, the forceps were washed in 30 mL of the normal saline and Cytospin preparation was done. To make recurrence models from cancer cell attached surgical instrument, three incisions were made in normal skin of each mouse, and local seeding was done by pinching subcutaneous tissue in 10, 20, 30 times each by using Adson teeth forceps mentioned above as cancer cell attached surgical instrument. Results: All skin cancers were squamous cell carcinoma. Local recurrences were developed in 7 mice (3 in 10 times forceping site, 2 in 20 times forceping and 3 in 30 times forceping). In the cytospin test, the mean number of squamous cells in 100 microscope was 28.6 in 10 times, 47.2 in 20 times, 93.6 in 30 times, respectively. P value was 0.002 in Wilcoxon-Sign test. Conclusion: The number of cell count was significantly increased as number of pinching was increased. And these cells are able to induce local recurrence by local seeding. Considering this result, authors are able to confirm that the minimal handling in cancer surgery is important factor to prevent local recurrence.

• Molecules and Cells
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• 제39권11호
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• pp.790-796
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• 2016

Dental pulp is a highly vascularized tissue requiring adequate blood supply for successful regeneration. In this study, we investigated the functional role of stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source for in vivo formation of vessel-like structures. Primarily isolated SHEDs showed mesenchymal stem cell (MSC)-like characteristics including the expression of surface antigens and in vitro osteogenic and adipogenic differentiation potentials. Moreover, SHEDs were positive for NG2, ${\alpha}$-smooth muscle actin (SMA), platelet-derived growth factor receptor beta ($PDGFR{\beta}$), and CD146 as pericyte markers. To prove feasibility of SHEDs as perivascular source, SHEDs were transplanted into immunodeficient mouse using Matrigel with or without human umbilical vein endothelial cells (HUVECs). Transplantation of SHEDs alone or HUVECs alone resulted in no formation of vessel-like structures with enough red blood cells. However, when SHEDs and HUVECs were transplanted together, extensive vessel-like structures were formed. The presence of murine erythrocytes within lumens suggested the formation of anastomoses between newly formed vessel-like structures in Matrigel plug and the host circulatory system. To understand underlying mechanisms of in vivo angiogenesis, the expression of angiogenic cytokine and chemokine, their receptors, and MMPs was compared between SHEDs and HUVECs. SHEDs showed higher expression of1VEGF, SDF-$1{\alpha}$, and $PDGFR{\beta}$ than HUVECs. On the contrary, HUVECs showed higher expression of VEGF receptors, CXCR4, and PDGF-BB than SHEDs. This differential expression pattern suggested reciprocal interactions between SHEDs and HUVECs and their involvement during in vivo angiogenesis. In conclusion, SHEDs could be a feasible source of perivascular cells for in vivo angiogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제30권5호
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• pp.438-443
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• 2004

Objectives : The proper development of the facial structures relies upon a sequence of tightly regulated signaling interactions between the ectoderm and mesoderm involving the participation of several families of signaling molecules. Among these, bone morphogenetic proteins (BMPs) have been suggested to be a key signal that regulates the development of the mandible and the initiation and morphogenesis of the teeth. The aim of this study was to examine the artificial development of the mandibular structures and to examine the role of BMPs on tooth morphogenesis and differentiation using an organ culture system. Materials and Methods : The tooth germs from Ed 11.5, 13.5 mice were dissected, and transplanted into the diastema of the mandible primordia. The mandibles containing the transplanted tooth germs were cultured in vitro. During this period, beads soaked with BMP4 were implanted around the transplanted tooth germs. In addition, a diastema block containing the transplanted tooth germ was dissected, then transferred to an adult mouse kidney. After the organ culture, the developing mandibular explant was removed from the kidney and prepared for the tissue specimens. Odontogeneis of the transplanted tooth germs was examined after Hematoxylin-eosin, Masson-trichrome staining. Results : Proliferation and differentiation of the tooth germs cultured in the diastema was observed. In the BMP4-treated tooth germs, the formation of the first and second molars was noted. The crown of the developing tooth showed the formation of a mature cusp with the deposition of enamel and dentin matrix. In conclusion, it was confirmed that BMP4 is involved in the formation of a dental crown and the differentiation of ameloblasts and odontoblasts of the molar tooth during the development of the transplanted tooth germs.

• International Journal of Oral Biology
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• 제42권4호
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• pp.169-174
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• 2017

Transient receptor potential melastatin 8 (TRPM8) plays a crucial role in innocuous cool sensation, acute cold pain and cold-induced hyperalgesia during pathologic conditions. To help understand TRPM8-mediated cold perception in the dental pulp and periodontal tissues, we examined the distribution of TRPM8-immunopositive (+) axons in molar and incisor pulp and periodontal tissues using transgenic mice expressing a genetically encoded axonal tracer in TRPM8+ neurons. In the radicular pulp of the molar teeth, a small number of TRPM8+ axons were observed. TRPM8+ axons branched frequently and extensively in the core of coronal pulp, forming a network in the peripheral pulp. Some TRPM8+ axons ascended between odontoblasts and were observed in the dentinal tubule. TRPM8+ axons were linear-shaped in the radicular pulp, whereas many TRPM8+ axons showed portions shaped like beads connected with thin axonal stands at the peripheral pulp. TRPM8 was densely expressed in the bead portions. In the incisor pulp, TRPM8+ axons were occasionally observed in the core of the coronal pulp and rarely observed at the peripheral pulp. TRPM8+ axons were occasionally observed and showed a linear shape rather than a bead-like appearance in the periodontal ligament and lamina propria of the gingival tissue. These findings, showing differential distribution of TRPM8+ axons between radicular and coronal portions of the molar pulp, between incisor and molar pulp, and between dental pulp and periodontal tissues, may reflect differential cold sensitivity in these regions.

• Molecules and Cells
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• 제46권10호
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• pp.627-636
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• 2023

Periodontal disease is a chronic inflammatory disease that leads to the gradual destruction of the supporting structures of the teeth including gums, periodontal ligaments, alveolar bone, and root cementum. Recently, interests in alleviating symptoms of periodontitis (PD) using natural compounds is increasing. Avenanthramide-C (Avn-C) is a polyphenol found only in oats. It is known to exhibit various biological properties. To date, the effect of Avn-C on PD pathogenesis has not been confirmed. Therefore, this study aimed to verify the protective effects of Avn-C on periodontal inflammation and subsequent alveolar bone erosion in vitro and in vivo. Upregulated expression of catabolic factors, such as matrix metalloproteinase 1 (MMP1), MMP3, interleukin (IL)-6, IL-8, and COX2 induced by lipopolysaccharide and proinflammatory cytokines, IL-1β, and tumor necrosis factor α (TNF-α), was dramatically decreased by Avn-C treatment in human gingival fibroblasts and periodontal ligament cells. Moreover, alveolar bone erosion in the ligature-induced PD mouse model was ameliorated by intra-gingival injection of Avn-C. Molecular mechanism studies revealed that the inhibitory effects of Avn-C on the upregulation of catabolic factors were mediated via ERK (extracellular signal-regulated kinase) and NF-κB pathway that was activated by IL-1β or p38 MAPK and JNK signaling that was activated by TNF-α, respectively. Based on this study, we recommend that Avn-C may be a new natural compound that can be applied to PD treatment.

• Journal of Periodontal and Implant Science
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• 제36권3호
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• pp.783-796
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• 2006

The periodontium is a topographically complex organ consisting of epithelial tissue, soft and mineralized tissues. Structures comprising the periodontium include the gingiva, periodontal ligament (PDL) , cementum and the alveolar bone. The molecular mechanism of differentiation in PDL fibroblast cells remain unclear. Amino acid transporters play an important role in supplying nutrition to normal and cancer cells and for cell proliferation. Amino acid transport system L is a major nutrient transport system responsible for the Na+-independent transport of neutral amino acids including several essential amino acids. The system L is divided into two major subgroups, the L-type amino acid transporter 1 (LAT1) and the L-type amino acid transporter 2 (LAT2). In this study, the expression pattern of amino acid transport system L was, therefore, investigated in the differentiation of PDL fibroblast cells. To determine the expression level of amino acid transport system L participating in intracellular transport of amino acids in the differentiation of PDL fibroblast cells, it was examined by RT-PCR, observation of cell morphology, Alizaline red-S staining and uptake analysis after inducing experimental differentiation in PDL fibroblast cells isolated from mouse molar teeth. The results are as follows. 1. The LAT1 mRNA was expressed in the early stage of PDL fibroblast cell differentiation. This expression level was gradually reduced by differentiation- inducing time and it was not observed after the late stage. 2. The expression level of LAT2 mRNA was increased in time-dependent manner during differentiation induction of PDL fibroblast cells. 3. There was no changes in. the expression level of 4F2hc mRNA, the cofactor of LAT1 and LAT2, during differentiation of PDL fibroblast cells. 4. The expression level of ALP mRNA was gradually increased and the expression level of Col I mRNA was decreased during differentiation of PDL fibroblast cells. 5. The L-leucine transport was reduced by time from the early stage to the late stage in PDL fibroblast cell differentiation. As the results, it is considered that among neutral ammo acid transport system L in differentiation of PDL fibroblast cells, the LATl has a key role in cell proliferation in the early stage of cell differentiation and the LAT2 has an important role in the late stage of cell differentiation for providing cells with neutral amino acids including several essential amino acids.

• 해부∙생물인류학
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• 제26권1호
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• pp.41-49
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• 2013

치아발생 및 형태형성 과정에서 치아상피와 치아간엽을 구성하는 세포는 동적인 세포주기의 변화가 일어난다. 현재까지 세포증식은 치아발생에 중요한 현상으로 알려져 있지만, 치아발생 중에 일어나는 복잡한 분자적 기전과 연관해서 세포주기의 각 시기가 어떻게 관여하는지에 대해서는 충분한 연구가 이루어지지 않았다. 그러므로 본 연구는 치아발생 기전과 세포주기의 시기의 변화와의 관계를 밝히고자 하였다. 치아발생 과정에서 일어나는 형태변화를 확인하기 위해 싹시기, 모자시기, 종시기의 쥐 앞니 및 어금니 치배를 헤마톡실린-에오신으로 염색하여 조직학적으로 관찰하였다. 또한 세포주기 시기의 표지자인 Ki-67, 싸이클린 A, 싸이클린 D1의 발현양상을 관찰하기 위해 면역조직화학염색을 시행하였다. 싹시기, 모자시기, 종시기에서 증식하는 세포들은 Ki-67과 싸이클린 A를 발현하는 것을 확인하였다. 싸이클린 D1은 앞니의 상아질모세포 및 모자시기의 사기질결절에서 특이적인 발현을 보였으며, 이곳에서는 Ki-67이나 싸이클린 A가 발현되지 않는다는 것을 발견하였다. 본 연구는 치아발생 중 각 주요 시기에서 세포주기의 변화를 관찰하였으며, 이는 치아발생에 관여하는 기전에 대한 중요한 정보를 제공한다. 또한 본 연구의 결과는 지금까지의 앞니의 사기질모세포 및 사기질결절의 특성에 대한 지식을 이해하는 데에 중요한 자료가 될 것으로 사료된다.