19 results on '"Hong, Jung-Min"'
Search Results
2. Hybrid scaffold composed of hydrogel/3D-framework and its application as a dopamine delivery system
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Kang, Kyung Shin, Lee, Soo-In, Hong, Jung Min, Lee, Jin Woo, Cho, Hwa Yeon, Son, Jin H., Paek, Sun Ha, and Cho, Dong-Woo
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- 2014
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3. Induction of Lrp5 HBM-causing mutations in Cathepsin-K expressing cells alters bone metabolism.
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Kang, Kyung Shin, Hong, Jung Min, Horan, Daniel J., Lim, Kyung-Eun, Bullock, Whitney A., Bruzzaniti, Angela, Hann, Steven, Warman, Matthew L., and Robling, Alexander G.
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COMPACT bone , *BONE metabolism , *OSTEOCLASTS , *BONE cells , *POPULATION density - Abstract
Abstract High-bone-mass (HBM)-causing missense mutations in the low density lipoprotein receptor-related protein-5 (Lrp5) are associated with increased osteoanabolic action and protection from disuse- and ovariectomy-induced osteopenia. These mutations (e.g. , A214V and G171V) confer resistance to endogenous secreted Lrp5/6 inhibitors, such as sclerostin (SOST) and Dickkopf homolog-1 (DKK1). Cells in the osteoblast lineage are responsive to canonical Wnt stimulation, but recent work has indicated that osteoclasts exhibit both indirect and direct responsiveness to canonical Wnt. Whether Lrp5-HBM receptors, expressed in osteoclasts, might alter osteoclast differentiation, activity, and consequent net bone balance in the skeleton, is not known. To address this, we bred mice harboring heterozygous Lrp5 HBM-causing conditional knock-in alleles to Ctsk-Cre transgenic mice and studied the phenotype using DXA, μCT, histomorphometry, serum assays, and primary cell culture. Mice with HBM alleles induced in Ctsk-expressing cells (TG) exhibited higher bone mass and architectural properties compared to non-transgenic (NTG) counterparts. In vivo and in vitro measurements of osteoclast activity, population density, and differentiation yielded significant reductions in osteoclast-related parameters in female but not male TG mice. Droplet digital PCR performed on osteocyte enriched cortical bone tubes from TG and NTG mice revealed that ~8–17% of the osteocyte population (depending on sex) underwent recombination of the conditional Lrp5 allele in the presence of Ctsk-Cre. Further, bone formation parameters in the midshaft femur cortex show a small but significant increase in anabolic action on the endocortical but not periosteal surface. These findings suggest that Wnt/Lrp5 signaling in osteoclasts affects osteoclastogenesis and activity in female mice, but also that some of the changes in bone mass in TG mice might be due to Cre expression in the osteocyte population. [ABSTRACT FROM AUTHOR]
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- 2019
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4. Pyk2 deficiency potentiates osteoblast differentiation and mineralizing activity in response to estrogen or raloxifene.
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Posritong, Sumana, Hong, Jung Min, Eleniste, Pierre P., McIntyre, Patrick W., Wu, Jennifer L., Himes, Evan R., Patel, Vruti, Kacena, Melissa A., and Bruzzaniti, Angela
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PROLINE , *OSTEOBLASTS , *RALOXIFENE , *BONE remodeling , *SELECTIVE estrogen receptor modulators , *CELLULAR signal transduction , *THERAPEUTICS - Abstract
Bone remodeling is controlled by the actions of bone-degrading osteoclasts and bone-forming osteoblasts (OBs). Aging and loss of estrogen after menopause affects bone mass and quality. Estrogen therapy, including selective estrogen receptor modulators (SERMs), can prevent bone loss and increase bone mineral density in post-menopausal women. Although investigations of the effects of estrogen on osteoclast activity are well advanced, the mechanism of action of estrogen on OBs is still unclear. The proline-rich tyrosine kinase 2 (Pyk2) is important for bone formation and female mice lacking Pyk2 (Pyk2-KO) exhibit elevated bone mass, increased bone formation rate and reduced osteoclast activity. Therefore, in the current study, we examined the role of estrogen signaling on the mechanism of action of Pyk2 in OBs. As expected, Pyk2-KO OBs showed significantly higher proliferation, matrix formation, and mineralization than WT OBs. In addition we found that Pyk2-KO OBs cultured in the presence of either 17β-estradiol (E2) or raloxifene, a SERM used for the treatment of post-menopausal osteoporosis, showed a further robust increase in alkaline phosphatase (ALP) activity and mineralization. We examined the possible mechanism of action and found that Pyk2 deletion promotes the proteasome-mediated degradation of estrogen receptor α (ERα), but not estrogen receptor β (ERβ). As a consequence, E2 signaling via ERβ was enhanced in Pyk2-KO OBs. In addition, we found that Pyk2 deletion and E2 stimulation had an additive effect on ERK phosphorylation, which is known to stimulate cell differentiation and survival. Our findings suggest that in the absence of Pyk2, estrogen exerts an osteogenic effect on OBs through altered ERα and ERβ signaling. Thus, targeting Pyk2, in combination with estrogen or raloxifene, may be a novel strategy for the prevention and/or treatment of bone loss diseases. [ABSTRACT FROM AUTHOR]
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- 2018
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5. Postnatal β-catenin deletion from Dmp1-expressing osteocytes/osteoblasts reduces structural adaptation to loading, but not periosteal load-induced bone formation.
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Kang, Kyung Shin, Hong, Jung Min, and Robling, Alexander G.
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CATENINS , *DENTIN , *OSTEOPOROSIS , *PROTEIN expression , *CELLULAR signal transduction , *BONE mechanics , *OSTEOCYTES , *LABORATORY mice - Abstract
Mechanical signal transduction in bone tissue begins with load-induced activation of several cellular pathways in the osteocyte population. A key pathway that participates in mechanotransduction is Wnt/Lrp5 signaling. A putative downstream mediator of activated Lrp5 is the nucleocytoplasmic shuttling protein β-catenin (βcat), which migrates to the nucleus where it functions as a transcriptional co-activator. We investigated whether osteocytic βcat participates in Wnt/Lrp5-mediated mechanotransduction by conducting ulnar loading experiments in mice with or without chemically induced βcat deletion in osteocytes. Mice harboring βcat floxed loss-of-function alleles (βcat f/f ) were bred to the inducible osteocyte Cre transgenic 10 kb Dmp1-CreERt2. Adult male mice were induced to recombine the βcat alleles using tamoxifen, and intermittent ulnar loading sessions were applied over the following week. Although adult-onset deletion of βcat from Dmp1-expressing cells reduced skeletal mass, the bone tissue was responsive to mechanical stimulation as indicated by increased relative periosteal bone formation rates in recombined mice. However, load-induced improvements in cross sectional geometric properties were compromised in recombined mice. The collective results indicate that the osteoanabolic response to loading can occur on the periosteal surface when β-cat levels are significantly reduced in Dmp1-expressing cells, suggesting that either (i) only low levels of β-cat are required for mechanically induced bone formation on the periosteal surface, or (ii) other additional downstream mediators of Lrp5 might participate in transducing load-induced Wnt signaling. [ABSTRACT FROM AUTHOR]
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- 2016
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6. A novel tissue-engineered trachea with a mechanical behavior similar to native trachea.
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Park, Jeong Hun, Hong, Jung Min, Ju, Young Min, Jung, Jin Woo, Kang, Hyun-Wook, Lee, Sang Jin, Yoo, James J., Kim, Sung Won, Kim, Soo Hyun, and Cho, Dong-Woo
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TISSUE engineering , *TRACHEA , *MECHANICAL behavior of materials , *CARTILAGE , *THREE-dimensional imaging - Abstract
A novel tissue-engineered trachea was developed with appropriate mechanical behavior and substantial regeneration of tracheal cartilage. We designed hollow bellows scaffold as a framework of a tissue-engineered trachea and demonstrated a reliable method for three-dimensional (3D) printing of monolithic bellows scaffold. We also functionalized gelatin sponge to allow sustained release of TGF-β1 for stimulating tracheal cartilage regeneration and confirmed that functionalized gelatin sponge induces cartilaginous tissue formation in vitro . A tissue-engineered trachea was then created by assembling chondrocytes-seeded functionalized gelatin sponges into the grooves of bellows scaffold and it showed very similar mechanical behavior to that of native trachea along with substantial regeneration of tracheal cartilage in vivo . The tissue-engineered trachea developed here represents a novel concept of tracheal substitute with appropriate mechanical behavior similar to native trachea for use in reconstruction of tracheal stenosis. [ABSTRACT FROM AUTHOR]
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- 2015
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7. Electromagnetically controllable osteoclast activity.
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Hong, Jung Min, Kang, Kyung Shin, Yi, Hee-Gyeong, Kim, Shin-Yoon, and Cho, Dong-Woo
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ELECTROMAGNETISM , *OSTEOCLASTS , *ELECTROMAGNETIC fields , *PHOSPHORYLATION , *INTEGRINS , *EXTRACELLULAR signal-regulated kinases - Abstract
Abstract: The time-varying electromagnetic field (EMF) has been widely studied as one of the exogenous stimulation methods for improving bone healing. Our previous study showed that osteogenic differentiation of adipose-derived stem cells was accelerated by a 45-Hz EMF, whereas a 7.5-Hz EMF inhibited osteogenic marker expression. Accordingly, we hypothesized that each negative and positive condition for the osteogenic differentiation could inversely influence osteoclast formation and differentiation. Here, we demonstrated that osteoclast formation, differentiation, and activity can be regulated by altering the frequency of the electromagnetic stimulation, such as 7.5 (negative for osteogenic differentiation) and 45Hz (positive for osteogenic differentiation). A 45Hz EMF inhibited osteoclast formation whereas a 7.5-Hz EMF induced differentiation and activity. Osteoclastogenic markers, such as NFATc1, TRAP, CTSK, MMP9, and DC-STAMP were highly expressed under the 7.5-Hz EMF, while they were decreased at 45Hz. We found that the 7.5-Hz EMF directly regulated osteoclast differentiation through ERK and p38 MAPK activation, whereas the EMF at 45Hz suppressed RANKL-induced phosphorylation of IκB. Additionally, actin ring formation with tubules and bone resorptive activity were enhanced at 7.5Hz through increased integrin β3 expression. However, these were inhibited at 45Hz. Although many questions remain unanswered, our study indicates that osteoclast formation and differentiation were controllable using physical tools, such as an EMF. It will now be of great interest to study the ill-defined correlation between electromagnetic conditions and osteoclast activities, which eventually could lead to determining the therapeutic characteristics of an EMF that will treat bone-related diseases. [Copyright &y& Elsevier]
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- 2014
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8. Inhibitory effects of obovatol on osteoclast differentiation and bone resorption.
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Kim, Hyun-Ju, Hong, Jung Min, Yoon, Hye-Jin, Kwon, Byoung-Mog, Choi, Je-Yong, Lee, In-Kyu, and Kim, Shin-Yoon
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OSTEOCLASTS , *CELL differentiation , *BONE resorption , *MACROPHAGES , *BONE marrow , *TRANSCRIPTION factors , *LIPOPOLYSACCHARIDES - Abstract
Abstract: Osteoclasts are polykaryons that have the unique capacity to degrade bone. Modulation of osteoclast formation and function is a promising strategy for the treatment of bone-destructive diseases. Here, we report that obovatol, a natural compound isolated from Magnolia obovata, inhibits receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation in vitro and inflammatory bone loss in vivo. We found that obovatol strongly inhibited osteoclast formation from bone marrow-derived macrophages in a dose-dependent manner without cytotoxicity. Obovatol significantly suppressed RANKL-induced activation of NF-κB, c-Jun-N-terminal kinase, and extracellular signal-regulated kinase signaling pathways. Obovatol also inhibited RANKL-induced expression of the genes c-Fos and nuclear factor of activated T cells c1, which are transcription factors important for osteoclastogenesis. In addition to osteoclast differentiation, obovatol blocked cytoskeletal organization and abrogated the bone resorbing activity of mature osteoclast. Obovatol also accelerated osteoclast apoptosis through the induction of caspase-3 activation. Consistent with its in vitro anti-resorptive effect, obovatol prevented bone loss induced by lipopolysaccharide in vivo. Together, our data suggest that obovatol may be a useful therapeutic agent for the treatment of pathological bone disorders characterized by excessive osteoclastic bone resorption. [Copyright &y& Elsevier]
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- 2014
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9. Enhanced endothelialization for developing artificial vascular networks with a natural vessel mimicking the luminal surface in scaffolds.
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Kang, Tae-Yun, Hong, Jung Min, Kim, Bum Jin, Cha, Hyung Joon, and Cho, Dong-Woo
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ENDOTHELIAL cells ,CELL metabolism ,ARTIFICIAL blood vessels ,VASCULAR grafts ,MIMICRY (Biology) ,TISSUE scaffolds - Abstract
Abstract: Large tissue regeneration remains problematic because of a lack of oxygen and nutrient supply. An attempt to meet the metabolic needs of cells has been made by preforming branched vascular networks within a scaffold to act as channels for mass transport. When constructing functional vascular networks with channel patency, emphasis should be placed on anti-thrombogenic surface issues. The aim of this study was to develop a rapid endothelialization method for creating an anti-thrombogenic surface mimicking the natural vessel wall in the artificial vascular networks. Shear stress preconditioning and scaffold surface modification were investigated as effective approaches for promoting biomaterial endothelialization. We found that a transient increase in shear stress at the appropriate time is key to enhancing endothelialization. Moreover, surface modification with bioactive materials such as collagen and recombinant mussel adhesive protein fused with arginine–glycine–aspartic acid peptide (MAP-RGD) showed a synergetic effect with shear stress preconditioning. Platelet adhesion tests demonstrated the anti-thrombogenic potential of MAP-RGD itself without endothelialization. The rapid endothelialization method established in this study can be easily applied to preformed artificial vascular networks in porous scaffolds. Development of artificial vascular networks with an anti-thrombogenic luminal surface will open up a new chapter in tissue engineering and regenerative medicine. [Copyright &y& Elsevier]
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- 2013
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10. Early growth response 2 negatively modulates osteoclast differentiation through upregulation of Id helix–loop–helix proteins
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Kim, Hyun-Ju, Hong, Jung Min, Yoon, Kyung-Ae, Kim, Nacksung, Cho, Dong-Woo, Choi, Je-Yong, Lee, In-Kyu, and Kim, Shin-Yoon
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OSTEOCLASTS , *ZINC-finger proteins , *TRANSCRIPTION factors , *LIGANDS (Biochemistry) , *T cells , *MACROPHAGE activation , *DNA-binding proteins , *IMMUNOPRECIPITATION - Abstract
Abstract: Early growth response 2 (Egr2) is a zinc finger transcription factor that acts as an important modulator of various physiological processes. In this study, we show that Egr2 negatively regulates receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. The overexpression of Egr2 in bone marrow-derived macrophages (BMMs) suppresses the formation of multinuclear osteoclasts and the expression of osteoclastogenic markers, including nuclear factor of activated T cells c1 (NFATc1). On the other hand, Egr2 overexpression does not impact the phagocytic activity of osteoclast precursors or the expression of macrophage-specific markers in the presence of the osteoclastogenic stimuli, RANKL and M-CSF. We further demonstrate that Egr2 induces the expression of the inhibitors of differentiation/DNA binding (Ids) helix–loop–helix (HLH) transcription factors, which are important repressors in RANKL-mediated osteoclastogenesis. Egr2 transactivates the Id2 promoter and increases its recruitment to the Id2 promoter region. In addition, Egr2-dependent induction of Id2 promoter activity, and its binding to the Id2 promoter is abrogated by the overexpression of the Egr2 repressor, NGFI-A binding protein 2 (Nab2). Accordingly, coexpression with Nab2 restores Egr2-mediated suppression of osteoclast differentiation. Furthermore, knockdown of Egr2 using shRNA enhances osteoclastogenesis and decreases Id2 gene expression. Ectopic expression of Id2 reverses the phenotype mediated by Egr2 silencing. Taken together, our results identify Egr2 as an important modulator of RANKL-induced osteoclast differentiation and provide the link between RANKL, Egr2 and Id proteins in osteoclast-lineage cells. [Copyright &y& Elsevier]
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- 2012
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11. Enhancement of bone regeneration through facile surface functionalization of solid freeform fabrication-based three-dimensional scaffolds using mussel adhesive proteins.
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Hong, Jung Min, Kim, Bum Jin, Shim, Jin-Hyung, Kang, Kyung Shin, Kim, Ki-Joo, Rhie, Jong Won, Cha, Hyung Joon, and Cho, Dong-Woo
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BONE regeneration ,SOLID freeform fabrication ,TISSUE engineering ,TISSUE scaffolds ,MUSSEL culture ,RECOMBINANT proteins ,SCANNING electron microscopy ,CELL proliferation ,BONE morphogenetic proteins - Abstract
Abstract: Solid freeform fabrication (SFF) is recognized as a promising tool for creating tissue engineering scaffolds due to advantages such as superior interconnectivity and highly porous structure. Despite structural support for SFF-based three-dimensional (3-D) scaffolds that can lead to tissue regeneration, lack of cell recognition motifs and/or biochemical factors has been considered a limitation. Previously, recombinant mussel adhesive proteins (MAPs) were successfully demonstrated to be functional cell adhesion materials on various surfaces due to their peculiar adhesive properties. Herein, MAPs were applied as surface functionalization materials to SFF-based 3-D polycaprolactone/poly(lactic-co-glycolic acid) scaffolds. We successfully coated MAPs onto scaffold surfaces by simply dipping the scaffolds into the MAP solution, which was confirmed through X-ray photoelectron spectroscopy and scanning electron microscopy analyses. Through in vitro study using human adipose tissue-derived stem cells (hADSCs), significant enhancement of cellular activities such as attachment, proliferation, and osteogenic differentiation was observed on MAP-coated 3-D scaffolds, especially on which fused arginine–glycine–aspartic acid peptides were efficiently exposed. In addition, we found that in vivo hADSC implantation with MAP-coated scaffolds enhanced bone regeneration in a rat calvarial defect model. These results collectively demonstrate that facile surface functionalization of 3-D scaffolds using MAP would be a promising strategy for successful tissue engineering applications. [Copyright &y& Elsevier]
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- 2012
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12. Polymorphisms in the Annexin gene family and the risk of osteonecrosis of the femoral head in the Korean population
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Kim, Tae-Ho, Hong, Jung Min, Shin, Eun-Soon, Kim, Hyun-Ju, Cho, Yoon Shin, Lee, Jong-Young, Lee, Sang-Han, Park, Eui Kyun, and Kim, Shin-Yoon
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GENETIC polymorphisms , *ANNEXINS , *OSTEONECROSIS , *BONE diseases , *FEMUR diseases , *KOREANS , *POPULATION genetics , *ETIOLOGY of diseases , *DISEASE risk factors , *DISEASES - Abstract
Abstract: Objective: The pathogenesis of osteonecrosis of the femoral head (ONFH) probably reflects multiple etiologies. Recent studies have explored associations between genetic mutations and/or polymorphisms and ONFH. Annexins (ANXs) have been implicated in many physiological functions, including blood coagulation, inflammation, apoptosis, as well as Ca2+ homeostasis in bone cells, all of which may be associated with ONFH. The aim of this study was to evaluate the possible association of AnnexinA (ANXA) family gene polymorphisms with ONFH. Methods: 52 SNPs from three genes of the ANXA family were selected from public databases and genotyped in 443 ONFH patients and 273 control subjects using the Affymetrix Targeted Genotyping 3 K Chip array. The association analysis of genotyped SNPs and haplotypes was performed with ONFH. Results: Among the polymorphisms tested of the ANXA family gene, the rs9324679, rs9324677, rs10037814, and rs11960458 SNPs of the ANXA6 gene were significantly associated with the risk of ONFH in all alternative analysis models (p range; 0.0007–0.049, odds ratio (OR); 0.63–1.72). Further analysis stratified by pathological etiology showed that these SNPs were also associated with the risk of ONFH in at least one subgroup (p range; 0.0017–0.049). Haplotype association analysis showed that several haplotypes were significantly associated with a risk of ONFH, with p values ranging between 0.0005 and 0.049 (OR range; 0.44–1.76). Conclusions: These findings indicate that the polymorphisms of ANXA6 are associated with ONFH. Thus, these polymorphisms may be useful genetic markers to identify high-risk individuals. [Copyright &y& Elsevier]
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- 2009
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13. Effects of radiopaque double antibiotic pastes on the proliferation, alkaline phosphatase activity and mineral deposition of dental pulp stem cells.
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Wu, Jennifer L., McIntyre, Patrick W., Hong, Jung Min, Yassen, Ghaeth H., and Bruzzaniti, Angela
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DENTAL pulp , *ALKALINE phosphatase , *STEM cells , *BARIUM sulfate , *ZIRCONIUM oxide - Abstract
• Intracanal medicaments promote the success of regenerative endodontic procedures. • The radiopaques BaSO 4 or ZrO 2 may allow for detecting medicaments in the root canal. • BaSO 4 or ZrO 2 added to DAP in methylcellulose did not affect DPSC proliferation. • The BaSO 4 DAP or ZrO 2 DAP medicaments increased ALP activity in DPSC. • Low DAP and short exposure times favor increased ALP and mineral deposition by DPSC. The aim of this study was to investigate the effects of two radiopaque agents, barium sulfate (BaSO 4) or zirconium oxide (ZrO 2) in double antibiotic paste (DAP), on the proliferation and mineral deposition of human dental pulp stem cells (DPSC). Radiopaque antimicrobial medicaments composed of methylcellulose (MC) thickening polymer with BaSO 4 or ZrO 2 and either 1 or 5 mg/mL DAP (equal portions of metronidazole and ciprofloxacin) were used to investigate DPSC proliferation after 3 days, and alkaline phosphatase (ALP) activity and mineral deposition after 7 and 14 days. Radiopaque agents without DAP and Ca(OH) 2 were used as controls. MC-BaSO 4 DAP and MC-ZrO 2 DAP at 1 or 5 mg/mL had no adverse effect on DPSC proliferation, compared to the media and MC controls. MC-ZrO 2 (DAP-free) greatly increased ALP activity after 7 days. DPSC mineral deposition was modestly reduced at 7 days by MC-BaSO 4 DAP and MC-ZrO 2 DAP, but not by DAP-free radiopaque agents, and was most reduced by 5 mg/mL DAP in the 14-day cultures. MC-BaSO 4 or MC-ZrO 2 medicaments containing up to 5 mg/mL of DAP supported the proliferation and early osteogenic differentiation of DPSC. Low DAP concentrations and short culture times led to more favorable effects on ALP activity and mineral deposition by DPSC. The findings suggest that radiopaque agents added for the purpose of detecting whether medicaments occupy the full extent of the root canal may have clinical applications. Radiopaque antibiotic medicaments containing low DAP concentrations may be an alternative to Ca(OH) 2 for regenerative endodontic procedures. [ABSTRACT FROM AUTHOR]
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- 2020
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14. Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass.
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Maupin, Kevin A., Himes, Evan R., Plett, Artur P., Chua, Hui Lin, Singh, Pratibha, Ghosh, Joydeep, Mohamad, Safa F., Abeysekera, Irushi, Fisher, Alexa, Sampson, Carol, Hong, Jung-Min, Childress, Paul, Alvarez, Marta, Srour, Edward F., Bruzzaniti, Angela, Pelus, Louis M., Orschell, Christie M., and Kacena, Melissa A.
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TRANSFORMING growth factors-beta , *BONE cells , *COMPACT bone , *BONE growth , *CANCELLOUS bone - Abstract
Osteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures. • Megakaryocytes and platelets increase with age but bone mass declines. • Megakaryocyte increase of osteoblasts and bone formation declines with age. • Aging decreases the response of bone cells to megakaryocytes. • Transplantation of old hematopoietic cells increases cortical bone expansion. • Transplantation of old hematopoietic cells increase trabecular bone parameters. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Desalted Salicornia europaea extract attenuated vascular neointima formation by inhibiting the MAPK pathway-mediated migration and proliferation in vascular smooth muscle cells.
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Won, Kyung Jong, Lee, Kang Pa, Baek, Suji, Cui, Long, Kweon, Mee-Hyang, Jung, Seung Hyo, Ryu, Yun-Kyoung, Hong, Jung Min, Cho, Eun-Ah, Shin, Hwa-Sup, and Kim, Bokyung
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SALICORNIA , *SMOOTH muscle physiology , *ETHYL acetate , *MITOGEN-activated protein kinases , *PHOSPHORYLATION , *PHYSIOLOGY , *THERAPEUTICS - Abstract
Salicornia europaea L. (SE) has been used as folk medicine for the treatment of various diseases such as obesity, diabetes, and cancer. However, its effects on atherosclerotic events in vascular smooth muscle cells (VSMCs) remain unknown. The present study explored the effects of the ethyl acetate fraction of desalted SE hot water extract (SEWEAF) on atherosclerotic responses (especially migration and proliferation) in VSMCs and vascular neointima formation. Treatment with the SEWEAF significantly suppressed the platelet-derived growth factor (PDGF)-BB-induced VSMC migration and proliferation as well the phosphorylation of mitogen-activated protein kinases (MAPKs) such as the p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2. Moreover, oral administration of the SEWEAF resulted in the attenuation of neointima formation in balloon-injured rat carotid arteries. Additionally, HPLC analysis showed that the major components in the two subfractions of the SEWEAF were five phenolic acids and four flavonols. In the SEWEAF components, for which atherosclerosis-linked responses in VSMCs have not been known, p -coumaric acid, quercetin-3-β- d -glucoside, and isorhamnetin-3-β- d -glucoside inhibited both PDGF-BB-induced migration and proliferation and isorhamnetin attenuated only PDGF-BB-stimulated VSMC proliferation. These results suggest that the SEWEAF may suppress PDGF-BB-induced VSMC migration by downregulating the phosphorylation of p38 MAPK and ERK1/2, thus leading to the reduction of neointimal hyperplasia during vascular remodeling. Therefore, the desalted SE extract, SEWEAF may be a potential ingredient for dietary supplements or nutraceuticals to ameliorate and/or prevent vascular remodeling-related disorders. [ABSTRACT FROM AUTHOR]
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- 2017
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16. The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss
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Kim, Tae-Ho, Jung, Ji Won, Ha, Byung Geun, Hong, Jung Min, Park, Eui Kyun, Kim, Hyun-Ju, and Kim, Shin-Yoon
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OSTEOPOROSIS in women , *FLAVONOIDS , *OVARIECTOMY , *BONE resorption , *CELL differentiation , *OSTEOCLAST inhibition , *BIOMARKERS , *TOMOGRAPHY , *ANIMAL models in research , *THERAPEUTICS - Abstract
Abstract: Flavonoids, a group of polyphenolic compounds abundant in plants, are known to prevent bone loss in ovariectomized (OVX) animal models. Inhibition of osteoclast differentiation and bone resorption is considered as an effective therapeutic approach in the treatment of postmenopausal bone loss. Luteolin, a plant flavonoid, has potent anti-inflammatory properties both in vivo and vitro. In this study, we found that luteolin markedly decreased the differentiation of both bone marrow mononuclear cells and Raw264.7 cells into osteoclasts. Luteolin also inhibited the bone resorptive activity of differentiated osteoclasts. We further investigated the effects of luteolin on ovariectomy-induced bone loss using micro-computed tomography, biomechanical tests and serum markers assay for bone remodeling. Oral administration of luteolin (5 and 20 mg/kg per day) to OVX mice caused significant increase in bone mineral density and bone mineral content of trabecular and cortical bones in the femur as compared to those of OVX controls, and prevented decreases of bone strength indexes induced by OVX surgery. Serum biochemical markers assays revealed that luteolin prevents OVX-induced increases in bone turnover. These data strongly suggest that luteolin has the potential for prevention of bone loss in postmenopausal osteoporosis by reducing both osteoclast differentiation and function. [ABSTRACT FROM AUTHOR]
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- 2011
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17. HSD11B1 polymorphisms predicted bone mineral density and fracture risk in postmenopausal women without a clinically apparent hypercortisolemia
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Hwang, Joo-Yeon, Lee, Seung Hun, Kim, Ghi Su, Koh, Jung-Min, Go, Min Jin, Kim, Young-Jin, Kim, Hyung-Cheol, Kim, Tae-Ho, Hong, Jung Min, Park, Eui Kyun, Lee, Jong-Young, and Kim, Shin-Yoon
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GENETIC polymorphisms , *GLUCOCORTICOIDS , *BONE density , *POSTMENOPAUSE , *OSTEOPOROSIS , *CORTISONE , *BONE metabolism - Abstract
Abstract: Introduction: Endogenous glucocorticoid (GC) may participate in bone physiology, even in subjects with no glucocorticoid excess. 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) is a primary regulator catalyzing the reduction of inactive cortisone to active cortisol. To elucidate genetic relevance of HSD11B1 variants to vertebral fracture and osteoporosis, we investigated the potential involvement of six HSD11B1 SNPs in postmenopausal women. Methods: All exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Six polymorphisms were selected and genotyped in all study participants (n =1329). BMD was measured using dual-energy X-ray absorptiometry. Results: HSD11B1 +16374C>T and +27447G>C were associated with reduced vertebral fracture risk (p =0.016 and 0.032, respectively). Two of these (LD block2) in intron 5 (rs1000283 and rs932335) were significantly associated with bone mineral density (BMD) at the femoral neck (p =0.00005 and 0.0002, respectively). Specifically, HSD11B1 +16374C>T and +27447G>C polymorphisms were associated with higher BMD values of the femoral neck in multiple comparison (p =0.0002 and 0.0004, respectively) and Bonferroni corrected significance level (97% power). Consistent with these results, HSD11B1-ht21 and -ht22 comprising both SNPs also showed the evidence of association with BMD values of the femoral neck (p domiant =0.0002 and p recessive =0.00005, respectively). Conclusion: Our results provide preliminary evidence supporting an association of HSD11B1 with osteoporosis in postmenopausal women. Also, these findings demonstrate that +16374C>T polymorphism may be useful genetic markers for bone metabolism. [Copyright &y& Elsevier]
- Published
- 2009
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18. Chloroquine increases osteoclast activity in vitro but does not improve the osteopetrotic bone phenotype of ADO2 mice.
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Alam, Imranul, Gerard-O'Riley, Rita L., Acton, Dena, Hardman, Sara L., Hong, Jung Min, Bruzzaniti, Angela, and Econs, Michael J.
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OSTEOCLASTS , *PHENOTYPES , *CHLOROQUINE , *BONE density , *OSTEOBLASTS , *PHENOTYPIC plasticity , *LUMBAR vertebrae , *CHLORIDE channels - Abstract
Autosomal Dominant Osteopetrosis type II (ADO2) is a bone disease of impaired osteoclastic bone resorption that usually results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene. We created mouse models of ADO2 by introducing a knock-in (p.G213R) mutation in the Clcn7 gene, which is analogous to one of the common mutations (G215R) found in humans. The mutation leads to severe osteopetrosis and lethality in homozygous mice but produces substantial phenotypic variability in heterozygous mice on different genetic backgrounds that phenocopy the human disease of ADO2. ADO2 is an osteoclast-intrinsic disease, and lysosomal enzymes and proteins are critical for osteoclast activity. Chloroquine (CQ) is known to affect lysosomal trafficking, intracellular signaling and the lysosomal and vesicular pH, suggesting it might improve ADO2 osteoclast function. We tested this hypothesis in cell culture studies using osteoclasts derived from wild-type (WT or ADO2+/+) and ADO2 heterozygous (ADO2+/−) mice and found that CQ and its metabolite desethylchloroquine (DCQ), significantly increased ADO2+/− osteoclasts bone resorption activity in vitro , whereas bone resorption of ADO2+/+ osteoclasts was increased only by DCQ. In addition, we exploited our unique animal model of ADO2 on 129 background to identify the effect of CQ for the treatment of ADO2. Female ADO2 mice at 8 weeks of age were treated with 5 doses of CQ (1, 2.5, 5, 7.5 and 10 mg/kg BW/day) via drinking water for 6 months. Bone mineral density and bone micro-architecture were analyzed by longitudinal in vivo DXA and micro-CT at baseline, 3 and 6 months. Serum bone biomarkers (CTX, TRAP and P1NP) were also analyzed at these time points. CQ treatment at the doses tested failed to produce any significant changes of aBMD, BMC (whole body, femur and spine) and trabecular BV/TV (distal femur) in ADO2 mice compared to the control group (water only). Further, levels of bone biomarkers were not significantly changed due to CQ treatment in these mice. Our findings indicate that while CQ increased osteoclast activity in vitro , it did not improve the osteopetrotic bone phenotypes in ADO2 heterozygous mice. • Chloroquine, a lysosomotropic agent, affects lysosomal trafficking and intracellular signaling. • Chloroquine increased osteoclast differentiation, size and bone resorption activity in vitro. • No significant changes of bone phenotypes observed in ADO2 mice treated with chloroquine. • Serum levels of bone biomarkers were similar due to chloroquine treatment in ADO2 mice. • Chloroquine did not improve the osteopetrotic phenotypes in ADO2 heterozygous micegep. [ABSTRACT FROM AUTHOR]
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- 2021
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19. Polymorphisms and haplotypes of integrinα1 (ITGA1) are associated with bone mineral density and fracture risk in postmenopausal Koreans
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Lee, Hye-Ja, Kim, Shin-Yoon, Koh, Jung-Min, Bok, Jung, Kim, Kwang-Joong, Kim, Kyung-Seon, Park, Mi-Hyun, Shin, Hyoung-Doo, Park, Byung Lae, Kim, Tae-Ho, Hong, Jung Min, Park, Eui Kyun, Kim, Duk Jae, Oh, Bermseok, Kimm, Kuchan, Kim, Ghi Su, and Lee, Jong-Young
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GENETIC polymorphisms , *BONE diseases , *VITAMIN D deficiency , *BONE injuries , *OSTEOPOROSIS , *OSTEOARTHRITIS - Abstract
Abstract: Introduction: ITGA1 is involved in the early remodeling of osteoarthritic cartilage and plays an essential role in the regulation of mesenchymal stem cell proliferation and cartilage production. We investigated the association between bone parameters and ITGA1 polymorphisms and their haplotype linkage disequilibrium (LD) blocks (BL_hts). Genetic susceptibility to osteoporosis was studied in 946 postmenopausal Korean women. Methods: We identified 67 genetic polymorphisms in ITGA1 region by direct sequencing (n =114). Eight SNPs were genotyped to further investigate their potential involvement in osteoporosis in postmenopausal women (n =946). Areal BMD of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry. Results: The SNPs, + 73187C > T (exon 3) and + 76969T > G (intron 5), and their BL_hts were associated with bone mineral density (BMD) at various femur sites (p =0.009–0.05). Moreover, + 159174A > C (intron 28) and its haplotype BL3_ht1 showed a highly significant association with risk of non-vertebral fracture (p =0.002–0.005) and the minor allele of + 159174A > C showed a protective effect. Conclusions: These results are suggestive of the association of ITGA1 with osteoporosis and related risk in postmenopausal women. [Copyright &y& Elsevier]
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- 2007
- Full Text
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