• Molecules and Cells
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• v.39 no.10
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• pp.734-741
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• 2016

Granulocyte-macrophage colony stimulating factor (GM-CSF) has a role in inducing emergency hematopoiesis upon exposure to inflammatory stimuli. Although GM-CSF generated murine bone marrow derived cells have been widely used as macrophages or dendritic cells in research, the exact characteristics of each cell population have not yet been defined. Here we discriminated GM-CSF grown bone marrow derived macrophages (GM-BMMs) from dendritic cells (GM-BMDCs) in several criteria. After C57BL/6J mice bone marrow cell culture for 7 days with GM-CSF supplementation, two main populations were observed in the attached cells based on MHCII and F4/80 marker expressions. GM-BMMs had $MHCII^{low}F4/80^{high}$ as well as $CD11c^+CD11b^{high}CD80^-CD64^+MerTK^+$ phenotypes. In contrast, GM-BMDCs had $MHCII^{high}F4/80^{low}$ and $CD11c^{high}CD8{\alpha}^-CD11b^+CD80^+CD64^-MerTK^{low}$ phenotypes. Interestingly, the GM-BMM population increased but GM-BMDCs decreased in a GM-CSF dose-dependent manner. Functionally, GM-BMMs showed extremely high phagocytic abilities and produced higher IL-10 upon LPS stimulation. GM-BMDCs, however, could not phagocytose as well, but were efficient at producing $TNF{\alpha}$, $IL-1{\beta}$, IL-12p70 and IL-6 as well as inducing T cell proliferation. Finally, whole transcriptome analysis revealed that GM-BMMs and GM-BMDCs are overlap with in vivo resident macrophages and dendritic cells, respectively. Taken together, our study shows the heterogeneicity of GM-CSF derived cell populations, and specifically characterizes GM-CSF derived macrophages compared to dendritic cells.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.9-18
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• 2016

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

• Journal of Acupuncture Research
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• v.24 no.5
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• pp.13-22
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• 2007

Objectives : The differentiation of osteoblasts is controlled by various growth factors and matrix protein expressed in bone. The aim of this study was to investigate the effects of many herbs medicine(KHBJs) for bone healing that induces osteogenic activity in human osteoblast-like SaOS-2 cells. Methods : The osteogenic effects of KHBJs were evaluated by using cell proliferation(WST-8) assay, alkaline phosphatase(ALP) activity assay, colorimetric analysis of vascular endothelial growth factor(VEGF) expression in human osteoblast like SaOS-2 cell. Also, osteogenic activity of KHBJ fractions(KHBJB and KHBJR) by activity guided fractionation were evaluated. Results : About 7 KHBJs had effect on the proliferation of osteoblast like SaOS-2 cells, and dose-dependently increased alkaline phosphatase(ALP) activity. KHBJs markedly increased expression for VEGF. Fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs on osteogenic activity in SaOS-2 cells. Conclusions: This study found that 7 KHBJs had effect on proliferation, ALP activity, and VEGF expression in osteoblast like SaOS-2 cells. These results propose that KHBJs can play an important role in osteoblastic bone formation, and may possibly lead to the development of bone-forming drugs.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2017.05a
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• pp.158-158
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• 2017

Titanium and its alloys have been used in the field dental and orthopedic implants because of their excellent mechanical properties and biocompatibility. Despite these attractive properties, their passive films were somewhat bioinert in nature so that sufficient adhesion of bone cells to implant surface was delayed after surgical treatment. Recently, plasma electrolyte oxidation (PEO) of titanium metal has attracted a great deal of attention is a comparatively convenient and effective technique and good adhesion to substrates and it enhances wear and corrosion resistances and produces thick, hard, and strong oxide coatings. Silicon(Si), Zinc(Zn), and Manganese(Mn) have a beneficial effect on bone. Si in particular has been found to be essential for normal bone and cartilage growth and development. And, Zn has been shown to be responsible for variations in body weight, bone length and bone biomechanical properties. Also, Mn influences regulation of bone remodeling because its low content in body is connected with the rise of the concentration of calcium, phosphates and phosphatase out of cells. The objective of this work was research on bone-like apatite morphology on Si-Zn-Mn-hydroxyapatite coating on Ti-6Al-4V alloy by plasma electrolytic oxidation. Anodized alloys were prepared at 280V voltage in the solution containing Si, Zn, and Mn ions. The surface characteristics of PEO treated Ti-6Al-4V alloy were investigated using XRD, FE-SEM, and EDS.

• Journal of Periodontal and Implant Science
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• v.35 no.4
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• pp.863-875
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• 2005

Bovine bone-derived bone substitutes are widely used for treatment of bone defects in dental and orthopedic regenerative surgery. The purpose of this study was to evaluate the basic characteristics of deproteinized bovine bone mineral as a bone graft substitute. Commercially available products from three different bovine bone minerals-Bio-Oss(GeistlichPharma, Switzerland), BBP(Oscotec. Korea), Osteograf/N-300(Dentsply Friadent Ceramed, USA) - were investigated. They were evaluated by scanning electron microscopy(SEM), energy dispersive X-ray spectrometer(EDS), surface area analysis(BET), and Kjeldahl protein analysis. Cell viability on different products was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT) assay. The results of this study indicated that each bone substitute displayed distinct surface properties. Furthermore, Kjeldahl protein analysis indicated that residual crude proteins are present in deproteinized bovine bone mineral. BBP showed relatively large amount of residual protein, which indicated that the possibility of disease transmission can not be safely ruled out. Based on the results of this study, it is suggested that active quality management is strongly needed in operations that involve processing bovine bone tissue for medical use.

• Clinical and Experimental Pediatrics
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• v.52 no.10
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• pp.1061-1068
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• 2009

The treatment of pediatric patients with chronic renal disease comprises management of nutritional imbalance, fluid, electrolyte, and acid-base disturbances, mineral bone disease, anemia, hypertension, and growth retardation. The treatment also includes administration of appropriate renal replacement therapy, if required. Adequate dietary intake of carbohydrates, fats, and proteins and caloric intake must be encouraged in such patients to ensure proper growth and development. In addition, fluid, electrolyte, and acid-base status must be regularly monitored and should be well maintained. Serum calcium, phosphorus, and parathyroid hormone levels must be maintained at their target range, which are determined on the basis of the glomerular filtration rate, to avoid the development of mineral bone disease. This can be achieved by using phosphorus binders and vitamin D analogues. An erythropoiesis-stimulating agent must be administered along with iron supplementation to maintain the hemoglobin level of the patients between 11-12 g/dL. Hypertension must be controlled with adequate water and sodium balance and appropriate antihypertensive agents. Administration of recombinant human growth hormone is recommended to improve the final adult heights.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.4
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• pp.365-370
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• 2006

Viral, bacterial and fungal infections can be transmitted via allografts such as bone, skin, cornea and cardiovascular tissues. Allogenic bone grafts have possibility of transmission of hepatitis C, human immunodeficiency virus (HIV-1), human T-Cell leukaemia virus (HTLV), tuberculosis and other bacterias. The tissue bank should have a policy for obtaining information from the patient's medical report as to whether the donor had risk factors for infectious diseases. Over the past several years, improvements in donor screening criteria, such as excluding potential donor with "high risk" for HIV-1 and hepatitis infection, and donor blood testing result in the reduction of transmission of these diseases. During tissue processing, many allografts are exposed to antibiotics, disinfectants and terminal sterilization such as irradiation, which further reduce or remove the risk of transmitting diseases. Because the effectiveness of some tissue grafts such as, fresh frozen osteochondral grafts, depends on cellular viability, not all can be subjected to sterilization and processing steps and, therefore, the risk of transmission of infectious disease remains. This article is review of the transmission of considering infectious disease in allogenic bone transplantation and the processing steps of reducing the risk. The risk of viral transmission in allografts can be reduced in several standards. The most important are donor-screening tests and the removal of blood and soft tissues by processing steps under the aseptic environment. In conclusion, final sterilizations including the irradiation, can be establish the safety of allografts.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.4
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• pp.395-398
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• 2008

Bisphosphonate are a class of drugs with a chemical structure which inhibit bone resorption, actually used for metastatic bone disease, osteoporosis, Paget's disease and multiple myeloma. Significant complication associated with their use is reported recently : mandibular and maxillary osteomyelitis or osteonecrosis. So we here report our case about the patient who was diagnosed of prostate cancer in 2004 April and treated with bisphosphonate(Zoledronic acid-$Zometa^{(R)}$, Novartis Co.) intravenously every 3 to 4weeks at a dose of 4mg to prevent bone metastasis, and also, the patient who came to the hospital due to the bony exposure of mandible and pain in 2006 November and was diagnosed osteomyelitis of mandible as a result of biopsy, bone scan, PET CT examination.

• Journal of Periodontal and Implant Science
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• v.52 no.5
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• pp.383-393
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• 2022

Purpose: Aloe-emodin (AE), a natural anthraquinone abundant in aloe plants and rhubarb (Rheum rhabarbarum), has long been used to treat chronic inflammatory diseases. However, AE's underlying mechanisms in periodontal inflammation have not been fully elucidated. Acidic mammalian chitinase (AMCase) is a potential biomarker involved in bone remodeling. This study aimed to evaluate AE's effect on periodontitis in rats and investigate AMCase expression. Methods: Eighteen Sprague-Dawley rats were separated into the following groups: healthy (group 1), disease (group 2), vehicle (group 3), AE high-dose (group 4), and AE low-dose (group 5). Porphyromonas gingivalis ligatures were placed in rats (groups 2-5) for 7 days. Groups 4 and 5 were then treated with AE for an additional 14 days. Saliva was collected from all groups, and probing pocket depth was measured in succession. Periodontal pocket tissues were subjected to histomorphometric analysis after the rats were sacrificed. Bone marrow-derived macrophages and murine macrophages were stimulated with receptor activator of nuclear factor-κB ligand (RANKL) and treated with different concentrations of AE. AMCase expression was detected from the analysis of saliva, periodontal pocket tissues, and differentiated osteoclasts. Results: Among rats with P. gingivalis-induced periodontitis, the alveolar bone resorption levels and periodontal pocket depth were significantly reduced after treatment with AE. AMCase protein expression was significantly higher in the disease group than in the healthy control (P<0.05). However, AE inhibited periodontal inflammation by downregulating AMCase expression in saliva and periodontal pocket tissue. AE significantly reduced RANKL-stimulated osteoclastogenesis by modulating AMCase (P<0.05). Conclusions: AE decreases alveolar bone loss and periodontal inflammation, suggesting that this natural anthraquinone has potential value as a novel therapeutic agent against periodontal disease.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.2
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• pp.138-146
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• 2022

Purpose: Children with celiac disease (CD) are at an increased risk of low bone mineral density (BMD) owing to malabsorption of fat-soluble vitamins, inflammation, and malnutrition. This study aimed to determine the prevalence and risk factors for low BMD in Iranian children with CD. Methods: This prospective cohort study examined 149 Iranian children with CD between 2011 and 2018 at Zabol University of Medical Sciences. BMD was measured using dual-energy X-ray absorptiometry. Demographic, clinical, and laboratory data were collected from patients' medical records. Logistic regression analysis was performed to identify the factors associated with low areal BMD (BMD-Z <-2) in the lumbar spine and femoral neck. Descriptive data were analyzed using the mean, standard deviation, and relative frequency. Data were analyzed using the chi-square test, t-test, and analysis of variance. Results: Of the 149 children with CD, 27.5% had osteoporosis. The mean body mass index (BMI) Z score was -1.28±1.2. Lower BMI was associated with a higher likelihood of BMD-Z (odds ratio 2.17; p≤0.05). Conclusion: Overall, the findings of this study showed that there was no correlation among Marsh classification, presence of specific human leukocyte antigens, and low BMD in Iranian children with CD. BMI can be a predictor of bone density in children with CD and may be applied clinically in early screenings to evaluate the bone health status in these children.