• Title/Summary/Keyword: Bone Development

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A Medium-Chain Fatty Acid, Capric Acid, Inhibits RANKL-Induced Osteoclast Differentiation via the Suppression of NF-κB Signaling and Blocks Cytoskeletal Organization and Survival in Mature Osteoclasts

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Kim, Shin-Yoon;Yoon, Young-Ran
    • Molecules and Cells
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    • v.37 no.8
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    • pp.598-604
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    • 2014
  • Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced $I{\kappa}B{\alpha}$ phosphorylation, p65 nuclear translocation, and NF-${\kappa}B$ transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.

Effect of recombinant human bone morphogenetic protein-2 on bisphosphonate-treated osteoblasts

  • Kwon, Taek-Kyun;Song, Jae-Min;Kim, In-Ryoung;Park, Bong-Soo;Kim, Chul-Hoon;Cheong, In-Kyo;Shin, Sang-Hun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.40 no.6
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    • pp.291-296
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    • 2014
  • Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphophonate therapy that has been reported in recent years. Osteoclastic inactivity by bisphosphonate is the known cause of BRONJ. Bone morphogenetic protein-2 (BMP-2) plays an important role in the development of bone. Recombinant human BMP-2 (rhBMP-2) is potentially useful as an activation factor for bone repair. We hypothesized that rhBMP-2 would enhance the osteoclast-osteoblast interaction related to bone remodeling. Materials and Methods: Human fetal osteoblast cells (hFOB 1.19) were treated with $100{\mu}M$ alendronate, and 100 ng/mL rhBMP-2 was added. Cells were incubated for a further 48 hours, and cell viability was measured using an MTT assay. Expression of the three cytokines from osteoblasts, receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL), osteoprotegerin (OPG), and macrophage colony-stimulating factor (M-CSF), were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: Cell viability was decreased to $82.75%{\pm}1.00%$ by alendronate and then increased to $110.43%{\pm}1.35%$ after treatment with rhBMP-2 (P<0.05, respectively). OPG, RANKL, and M-CSF expression were all decreased by alendronate treatment. RANKL and M-CSF expression were increased, but OPG was not significantly affected by rhBMP-2. Conclusion: rhBMP2 does not affect OPG gene expression in hFOB, but it may increase RANKL and M-CSF gene expression.

Bone Health Evaluations and Secondary Fragility Fractures in Hip Fracture Patients

  • Emily M. Pflug;Ariana Lott;Sanjit R. Konda;Philipp Leucht;Nirmal Tejwani;Kenneth A. Egol
    • Hip & pelvis
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    • v.36 no.1
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    • pp.55-61
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    • 2024
  • Purpose: This study sought to examine the utilization of bone health evaluations in geriatric hip fracture patients and identify risk factors for the development of future fragility fractures. Materials and Methods: A consecutive series of patients ≥55 years who underwent surgical management of a hip fracture between September 2015 and July 2019 were identified. Chart review was performed to evaluate post-injury follow-up, performance of a bone health evaluation, and use of osteoporosis-related diagnostic and pharmacologic treatment. Results: A total of 832 patients were included. The mean age of the patients was 81.2±9.9 years. Approximately 21% of patients underwent a comprehensive bone health evaluation. Of this cohort, 64.7% were started on pharmacologic therapy, and 73 patients underwent bone mineral density testing. Following discharge from the hospital, 70.3% of the patients followed-up on an outpatient basis with 95.7% seeing orthopedic surgery for post-fracture care. Overall, 102 patients (12.3%) sustained additional fragility fractures within two years, and 31 of these patients (3.7%) sustained a second hip fracture. There was no difference in the rate of second hip fractures or other additional fragility fractures based on the use of osteoporosis medications. Conclusion: Management of osteoporosis in geriatric hip fracture patients could be improved. Outpatient follow-up post-hip fracture is almost 70%, yet a minority of patients were started on osteoporosis medications and many sustained additional fragility fractures. The findings of this study indicate that orthopedic surgeons have an opportunity to lead the charge in treatment of osteoporosis in the post-fracture setting.

Current insights into inherited bone marrow failure syndromes

  • Chung, Nack-Gyun;Kim, Myungshin
    • Clinical and Experimental Pediatrics
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    • v.57 no.8
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    • pp.337-344
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    • 2014
  • Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients.

Improvement of Glaze Hardness in Commercial Bone China

  • Kim, Hyeong-Jun;Han, Yoon Soo;Kim, Dong-Hwan;Kim, Da-Mi;Choi, Jae-Ho;Lee, Sung-Min;Kim, Yoojin;Kim, Hyung-Tae
    • Journal of the Korean Ceramic Society
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    • v.52 no.6
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    • pp.508-513
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    • 2015
  • In order to improve the hardness of commercial bone china, we attempted to control the glost firing temperature and apply a chemical strengthening process. When the glost firing time was longer or its temperature was higher than normal conditions, the hardness was improved by approximately 5%. The chemical strengthening process also enhanced the hardness of the glaze by more than 13% compared with bone china. It is believed that the enhancement of the hardness of the glaze was related to the development of residual compressive stress in the glaze due to 1) the increase in the calcium phosphate phase in the interface layer between the body and the glaze after firing, and 2) the increase of the $K^+$ concentration on the glaze surface during the chemical strengthening process.

Development of the Osseo-integrated Implant system for Laboratory Animals (동물실험용 골융합 임플란트 시스템 개발)

  • Bae, Tae-Soo;Heo, Hyun;Kim, Shin-Ki;Mun, Mu-Seong;Ahn, Jae-Yong;Hong, Sung-Ran
    • Journal of the Korean Society for Precision Engineering
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    • v.24 no.10
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    • pp.117-122
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    • 2007
  • The novel implant system was developed using osseo-integration technology which enable amputee to overcome skin troubles in use of previous socket system and was evaluated in view of biomechanics, radiology, histology, and pathology. The osseo-integrated implants were designed and manufactured using CT image of canine's tibia and were applied to laboratory animals (canines). The follow-up studies were performed for 24 months with 10 canines. In radiology examination, we found that the relative low strain distribution caused medial and posterior bone resorption and then we verified them by biomechanical testing. In histological approach, the complete osseo-integration was observed through the activity of osteoblast cells around bone-implant interface and the radial outer region of bone due to peristeum reaction. Lastly in pathological aspect, the evidence of superficial infection was detected but that of deep infection was not. Therefore it is thought that infection problem will be overcome by immunity of body and good hygiene.

Chronic Myeloid Leukemia - Prognostic Value of Mutations

  • Kaleem, Bushra;Shahab, Sadaf;Ahmed, Nuzhat;Shamsi, Tahir Sultan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7415-7423
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    • 2015
  • Chronic myeloid leukemia (CML) is a stem cell disorder characterized by unrestricted proliferation of the myeloid series that occurs due to the BCR-ABL fusion oncogene as a result of reciprocal translocation t(9;22) (q34;q11). This discovery has made this particular domain a target for future efforts to cure CML. Imatinib revolutionized the treatment options for CML and gave encouraging results both in case of safety as well as tolerability profile as compared to agents such as hydroxyurea or busulfan given before Imatinib. However, about 2-4% of patients show resistance and mutations have been found to be one of the reasons for its development. European Leukemianet gives recommendations for BCR-ABL mutational analysis along with other tyrosine kinase inhibitors (TKIs) that should be administered according to the mutations harbored in a patient. The following overview gives recommendations for monitoring patients on the basis of their mutational status.

Effect of Body Composition and Osteoporosis Self-efficacy on Bone Mineral Density of Female Nursing Students (간호대학생의 신체조성과 골다공증 자기효능감이 골밀도에 미치는 영향)

  • Lee, Kyu Eun;Kim, Nam Sun
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.20 no.3
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    • pp.230-238
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    • 2013
  • Purpose: This study was done to identify the relationship among bone mineral density (BMD), body composition and osteoporosis self-efficacy and to identify predictors of BMD in female nursing students. Method: Participants were 154 nursing students. Osteoporosis self-efficacy was determined by a self-report questionnaire. BMD was measured by ultrasound bone densitometry and body composition by a body composition analyzer. Data were collected between April 1 and 27, 2013 and analyzed using descriptive statistics, ANOVA, Scheff$\acute{e}$ test, Pearson correlation coefficient, and multiple regression with SPSS 18.0. Results: Mean BMD at the calcaneus site was $0.58{\pm}1.31$ (T-score). Incidence of osteopenia was 11.7%. Percentage of body fat (PBF)-defined obesity had higher prevalence than body mass index (BMI)-defined obesity. BMD had significant positive correlations with skeletal muscle mass (r=.226, p=.005) and fat free mass (r=.225, p=.005). The factor predicting BMD was skeletal muscle mass with 4.7% of explained variance. Conclusion: Study results indicate that of body composition components, skeletal muscle mass is the prime predicting factor for BMD. Thus to promote healthy bones, it is important to strengthen the muscles using a program, based on balanced development of all muscles.

The Efficacy of Shikonin on Cartilage Protection in a Mouse Model of Rheumatoid Arthritis

  • Kim, Young-Ock;Hong, Seung-Jae;Yim, Sung-Vin
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.4
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    • pp.199-204
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    • 2010
  • The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.

Development of Refolding Process to Obtain Active Recombinant Human Bone Morphogenetic Protein-2 and its Osteogenic Efficacy on Oral Stem Cells

  • Lee, Ji-Hye;Jang, Young-Joo
    • International Journal of Oral Biology
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    • v.42 no.2
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    • pp.71-78
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    • 2017
  • BMP-2 is a well-known TGF-beta related growth factor, having a significant role in bone and cartilage formation. It has been employed to promote bone formation in some clinical trials, and to differentiate mesenchymal stem cells into osteoblasts. However, it is difficult to obtain this protein in its soluble and active form. hBMP-2 is expressed as an inclusion body in the bacterial system. To continuously supply hBMP-2 for research, we optimized the refolding of recombinant hBMP-2 expressed in E. coli, and established an efficient method by using detergent and alkali. Using a heparin column, the recombinant hBMP-2 was purified with the correct refolding. Although combinatorial refolding remarkably enhanced the solubility of the inclusion body, a higher yield of active dimer form of hBMP-2 was obtained from one-step refolding with detergent. The refolded recombinant hBMP-2 induced alkaline phosphatase activity in mouse myoblasts, at $ED_{50}$ of 300-480ng/ml. Furthermore, the expressions of osteogenic markers were upregulated in hPDLSCs and hDPSCs. Therefore, using the process described in this study, the refolded hBMP-2 might be cost-effectively useful for various differentiation experiments in a laboratory.