Yonsei Fraunhofer IZFP Medical Device Lab YFMED

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  • Publication
    Intensive morphometric analysis of enormous alterations in skeletal bone system with micro-CT for AHNAK−/− mice
    ( 2020)
    Kim, I.Y.
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    Yi, S.S.
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    Shin, J.H.
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    Kim, Y.N.
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    Ko, C.-Y.
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    Kim, H.S.
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    Lee, S.Y.
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    Bae, Y.S.
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    Seong, J.K.
    AHNAK has been reported to be involved in actin cytoskeleton rearrangement of some cell types, calcium homeostasis, and activation of T cells. Although the functional role of AHNAK in muscle cells, epidermis, and brain has been determined, its association with apparent clinical impairment has not been found yet. During phenotypic analysis of AHNAK knock out (KO) mice for many years, we observed that AHNAK KO mice showed very slow growth. Snouts of these animals were very short, and their bones were easily broken compared to normal mice. It is known that AHNAK is closely related to calcium. However, intensive morphological studies on phenotypes of bone have yet been reported for AHNAK. Thus, the objective of the present study was to analyze the morphology of skull, mandibular, limbs, and caudal bones of AHNAK KO mice intensively using micro-CT with many factors for various ages of these mice (6 weeks, 18 weeks, and 40 weeks). As a result, it was found that the facial region of AHNAK KO mouse showed a large difference in mandible than skull. Their both femur and tibia were shortened, and bone strength was also significantly decreased compared to normal mice. Particularly, the tail bone of AHNAK KO mice exhibited morphological abnormality by age. Taken together, these results suggest that AHNAK plays an important role in bone shape, development, and metabolism. Although our results demonstrated that AHNAK has a distinct role in bone, further investigations are needed to determine various features of bone metabolism related to AHNAK in the future.
  • Publication
    Data of intracellular insulin protein reduced by autophagy in INS-1E cells
    ( 2016)
    Kim, H.S.
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    Yoo, Y.-M.
    Autophagy appears to be involved in maintaining normal intracellular insulin content by accelerating the insulin degradation rate in β-cells (Marsh et al., 2007) [1]. 2-deoxy-d-glucose (2-DG) is metabolized by hexokinase, and acts as an inhibitor of glycolysis. 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways (Aghaee et al., 2012) [2], and appears to be an ideal tool for studying autophagy. Rapamycin induced upregulation of autophagy in both cultured isolated islets and pancreatic β-cells (Tanemura et al., 2012) [3]. Here, we examined that 2-DG or rapamycin-induced autophagy may decrease the production of intracellular insulin in INS-1E insulinoma cells. Data showed that autophagy was increased by 2-DG or rapamycin by Western blotting and Immunofluorescence staining analyses. Also, intracellular insulin decreased by 2-DG or rapamycin. Furthermore, the autophagy inhibitors, bafilomycin A1 and/or 3-methyladenine, in the presence o r absence of 2-DG or rapamycin increased intracellular insulin in INS-1E insulinoma cells.
  • Publication
    Antiangiogenic Activity of Acer tegmentosum Maxim Water Extract in Vitro and in Vivo
    ( 2015)
    Kim, E.C.
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    Kim, S.H.
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    Piao, S.J.
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    Kim, T.J.
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    Bae, K.
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    Kim, H.S.
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    Hong, S.S.
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    Lee, B.I.
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    Nam, M.
    Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway.
  • Publication
    Enhancement of bone quality and longitudinal growth due to free-fall motion in growing rats
    ( 2015)
    Cho, S.
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    Eom, S.
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    Seo, D.-H.
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    Park, J.
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    Ko, C.-Y.
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    Kim, H.S.
    Objectives: This study is to investigate the synchronous phenomena between bone quality and longitudinal length in a same subject affected by landing exercise. Physical exercise on the ground induces external loading to human body due to resistance from ground which can activate bone generation or remodeling. Especially, when the impact stimulation is applied to bone, it may improve bone quality and lengthening. Methods: 6-week-old male Wistar rats were randomly allocated to one of two conditions: free fall from 40 cm-height (I40; n = 7), and control (IC; n = 7). The impact stimulations were administered to the free fall groups, 10 times/day, and 5 days/week for 8 weeks. Structural parameters and longitudinal length of tibia were measured to quantitatively evaluate the variation in morphological characteristics and bone length with maturing. Results: The landing impact seems to be commonly effective on the enhancement of bone quality as well as longitudinal growth. Howe ver, the extent of enhancement may be more dominant in bone quality than longitudinal growth. On the other hand, the ratio of longitudinal growth seems to be dependent on the duration of stimuli whereas the enhancement of bone quality does not. Conclusions: This study verified that free-falls exercise can be effective on the enhancement of bone qualities and promotion of vertical growth in long bones. We expect that it might be possible for the moderate impact stimulation to be proposed as an aid for prevention of bone loss and promotion of bone lengthening. © 2015, Korean Society of Medical and Biological Engineering and Springer.
  • Publication
    Decreased bone volume and bone mineral density in the tibial trabecular bone is associated with Per2 gene by 405 nm laser stimulation
    ( 2015)
    Yoo, Y.-M.
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    Lee, M.-H.
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    Park, J.H.
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    Seo, D.-H.
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    Lee, S.
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    Jung, B.
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    Kim, H.S.
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    Bae, K.
    Low-level laser therapy/treatment (LLLT) using a minimally invasive laser needle system (MILNS) might enhance bone formation and suppress bone resorption. In this study, the use of 405 nm LLLT led to decreases in bone volume and bone mineral density (BMD) of tibial trabecular bone in wild-type (WT) and Per2 knockout (KO) mice. Bone volume and bone mineral density of tibial trabecular bone was decreased by 405 nm LLLT in Per2 KO compared to WT mice at two and four weeks. To determine the reduction in tibial bone, mRNA expressions of alkaline phosphatase (ALP) and Per2 were investigated at four weeks after 405 nm laser stimulation using MILNS. ALP gene expression was significantly reduced in the LLLT-stimulated right tibial bone of WT and Per2 KO mice compared to the non-irradiated left tibia (p < 0.001). Per2 mRNA expression in WT mice was significantly reduced in the LLLT-stimulated right tibial bone compared to the non-irradiated left tibia (p < 0.001). To identify the decrease in tibial bone mediated by the Per2 gene, levels of runt-related transcription factor 2 (Runx2) and ALP mRNAs were determined in non-irradiated WT and Per2 KO mice. These results demonstrated significant downregulation of Runx2 and ALPmRNA levels in Per2 KO mice (p < 0.001). Therefore, the reduction in tibial trabecular bone resulting from 405 nm LLLT using MILNS might be associated with Per2 gene expression.
  • Publication
    Effect of stool height on slumped posture during push-and-pull weeding motion
    ( 2015)
    Cho, Y.K.
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    Myeong, S.-S.
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    Cho, S.
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    Kim, H.S.
    Purpose: The excessive accumulation of work burden is one of the main factors underlying musculoskeletal disorders in the farming population. The present study was carried out to determine the joint torques and muscle contractions of the lower body in relation to slumped postures with or without a stool during push-and-pull weeding motions. Methods: Using data from a 3D motion analysis system, a 3D virtual human body model was created consisting of 19 segments and 59 muscles. Among these, the lower body joints (ankle, knee, hip, and lumbar) and muscles (tibialis anterior, gastrocnemius, biceps femoris, and erector spinae) were analyzed for four cases of slumped postures: without a stool and with stools of various heights (10, 15, and 20 cm). Results: The flexion of the lumbar joint was presented during push-and-pull weeding motions without a stool. However, the extension of the lumbar joint was presented during pushand-pull weeding motions with a stool. The ranges of th e joint torques did not change in a meaningful way between the results for the cases without a stool and with a stool. In addition, the results according to the stool height did not present meaningful outcomes associated with the angle change in the joints. Conclusions: Irrespective of the height, a stool may provide support for slumped postures involving the lumbar joint and erector spinae.
  • Publication
    Prediction of antiarthritic drug efficacies by monitoring active matrix metalloproteinase-3 (MMP-3) levels in collagen-induced arthritic mice using the MMP-3 probe
    ( 2014)
    Lee, A.
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    Park, K.
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    Choi, S.J.
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    Seo, D.-H.
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    Kim, K.
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    Kim, H.S.
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    Choi, K.
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    Kwon, I.C.
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    Yoon, S.-Y.
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    Youn, I.
    Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when drugs were applied. The decrease in RA scores in drug-treated CIA mice led to fluorescence reductions, mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X-ray, and histology results clearly showed marked decreases in bone and cartilage destruction, which were consistent with the reduction of fluorescence by down-regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit could be used to detect and monitor the active form of MMP-3 in CIA mice serum during a treatment course and thereby used to predict the drug response or resistance to RA therapies at an earlier stage. We hope that monitoring of active MMP-3 levels in arthritis patients using the MMP-3 diagnostic kit will be a promising tool for drug discovery, drug development, and monitoring of drug responses in RA therapy.
  • Publication
    Deterioration of trabecular bone microarchitecture in the lumbar vertebrae in growing male mice following sciatic neurectomy
    ( 2014)
    Ko, C.Y.
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    Jung, Y.J.
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    Seo, D.H.
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    Lee, S.D.
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    Kim, H.S.
    Sciatic nerve injury (SNI) can lead to significant bone loss in the lower extremities. However, the effects of SNI on the lumbar vertebrae are controversial. The present study aimed to evaluate the longitudinal effects of SNI on the lumbar vertebrae. Twenty-four 12-week-old male C57BL/6 mice (24.55 +/- 0.17 g) were randomly assigned to 3 groups (8 mice each) and underwent unilateral sciatic neurectomy (USN group), bilateral sciatic neurectomy (BSN group), or no surgery (CON group). The third (L3) and fourth (L4) lumbar vertebrae were scanned by in-vivo micro-computed tomography (Anot signCT) preoperatively and at 14 and 28 days postoperatively. Using mu CT images, structural parameters and bone mineralization density distribution of the trabecular bone were analyzed among the 3 groups. In the BSN group, structural and material properties of L3 and L4 worsened after 14 days. Deterioration in the structural properties of L3 was observed at 28 days in the USN group, whereas no changes were observed in L4. These results implied that SNI can cause considerable deterioration in the microarchitecture of trabecular bone in the lumbar vertebrae. However, differences in the magnitude and rate of the deterioration and its onset period are observed between cases of unilateral and bilateral SNI.
  • Publication
    Comparative study of hydroxyapatite prepared from seashells and eggshells as a bone graft material
    ( 2014)
    Lee, S.-W.
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    Balázsi, C.
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    Balázsi, K.
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    Seo, D.-H.
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    Kim, H.S.
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    Kim, C.-H.
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    Kim, S.-G.
    The aims of this study were to determine the physical properties of hydroxyapatite from seashells (sHA) and from eggshells (eHA), to analyze elements within sHA and eHA, and to compare the bone regeneration ability between sHA and eHA in a rat parietal bone defect model. The sHA and eHA particles had a similar morphology in scanning electron microscope images. From the Fourier-transform infrared absorbance spectra and X-ray diffraction results, both types of hydroxyapatite (HA) had the characteristics of pure HA. Inductively coupled plasma atomic emission spectroscopy results suggested that the sHA had higher levels of sodium and strontium than the eHA, whereas the eHA had higher levels of magnesium than the sHA. In -CT results, the mean bone mineral density of the sHA was significantly higher than the control at 4 weeks after the operation (p = 0.012). The mean bone volume of the eHA was significantly higher than the control at 8 weeks after the operation (p = 0.012). In the histological images at 4 weeks after the operation, foreign body multinucleated giant cells were observed around the agglomerated sHA particles, while there were fewer inflammatory reactions around the agglomerated eHA particles. The eHA group showed better results in bone formation than did the sHA group in this study.
  • Publication
    Water extract of the fruits of Alpinia oxyphylla inhibits osteoclast differentiation and bone loss
    ( 2014)
    Ha, H.
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    Shim, K.-S.
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    Kim, T.
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    Lee, C.-J.
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    Park, J.H.
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    Kim, H.S.
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    Ma, J.Y.
    Background: Excessive bone resorption by osteoclasts causes pathological bone destruction, seen in various bone diseases. There is accumulating evidence that certain herbal extracts have beneficial effects on bone metabolism. The fruits of Alpinia oxyphylla has been traditionally used for the treatment of diarrhea and enuresis. In this study, we investigated the effects of water extract of the fruits of Alpinia oxyphylla (WEAO) on osteoclast differentiation and osteoclast-mediated bone destruction.Methods: For osteoclast differentiation assay, mouse bone marrow-derived macrophages (BMMs) were cultured in the presence of RANKL and M-CSF. RANKL signaling pathways and gene expression of transcription factors regulating osteoclast differentiation were investigated by real-time PCR and Western blotting. A constitutively active form of NFATc1 was retrovirally transduced into BMMs. Bone resorbing activity of mature osteoclast was examined on a plate coated with an inorganic cr ystalline calcium phosphate. The in vivo effect against bone destruction was assessed in a murine model of RANKL-induced osteoporosis by micro-computed tomography and bone metabolism marker analyses.Results: WEAO dose-dependently inhibited RANKL-induced osteoclast differentiation from BMMs by targeting the early stages of osteoclast differentiation. WEAO inhibited RANKL-induced expression of NFATc1, the master regulator of osteoclast differentiation. Overexpression of a constitutively active form of NFATc1 blunted the inhibitory effect of WEAO on osteoclast differentiation, suggesting that NFATc1 is a critical target of the inhibitory action of WEAO. WEAO inhibited RANKL-induced expression of c-Fos, an upstream activator of NFATc1, by suppressing the classical NF-B signaling pathway. WEAO also inhibited RANKL-induced down-regulation of Id2 and MafB, negative regulators of NFATc1. WEAO does not directly affect bone resorbing activity of mature osteoclasts. In accordance with the in vitro results, WEA