• Title/Summary/Keyword: Bone biology

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Biological characteristics of osteoporosis drugs: the effect of osteoblast-osteoclast coupling

  • Kim, Sung-Jin;Moon, Seok Jun;Seo, Jeong Taeg
    • International Journal of Oral Biology
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    • v.44 no.1
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    • pp.1-7
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    • 2019
  • Osteoporosis is a common disease characterized by bone mass reduction, leading to an increased risk of bone fracture, and it is caused by an imbalance of osteoblastic bone formation and osteoclastic bone resorption. Current osteoporosis drugs aim to reduce the risk of bone fracture, either by increasing osteoblastic bone formation or decreasing osteoclastic bone resorption. However, osteoblasts and osteoclasts are closely coupled, such that any reagent altering the differentiation or activity of one eventually affects the other. This tight coupling between osteoblasts and osteoclasts not only limits the therapeutic efficacy but also threatens the safety of osteoporosis drugs. This review will discuss the biological mechanisms of action of currently approved medications for osteoporosis treatment, focusing on the osteoblast-osteoclast coupling.

Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice

  • Kang, Jung Yun;Kang, Namju;Shin, Dong Min;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.45 no.3
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    • pp.126-133
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    • 2020
  • Homer proteins are scaffold proteins that regulate calcium (Ca2+) signaling by modulating the activity of multiple Ca2+ signaling proteins. In our previous report, Homer2 and Homer3 regulated NFATc1 function through its interaction with calcineurin, which then acted to regulate receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone metabolism. However, to date, the role of Homers in osteoclastogenesis remains unknown. In this study, we investigated the roles of Homer2 and Homer3 in aging-dependent bone remodeling. Deletion of Homer2/Homer3 (Homer2/3 DKO) markedly decreased the bone density of the femur. The decrease in bone density was not seen in mice with Homer2 (Homer2-/-) and Homer3 (Homer3-/-) deletion. Moreover, RANKL treatment of bone marrow-derived monocytes/macrophages in Homer2/3 DKO mice significantly increased the formation of multinucleated cells and resorption areas. Finally, Homer2/3 DKO mice decreased bone density in an aging-dependent manner. These findings suggest a novel potent mode of bone homeostasis regulation through osteoclasts differentiation during aging by Homer proteins, specifically Homer2 and Homer3.

1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation

  • Hyoeun Jeon;Jungeun Yu;Jung Me Hwang;Hye-Won Park;Jiyeon Yu;Zee-Won Lee;Taesoo Kim;Jaerang Rho
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.43.1-43.12
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    • 2022
  • Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

Effects of Silkworm Pupae on Bone Mineral Density in Ovariectomized Rat Model of Osteoporesis

  • Ryu, Kang-Sun;Lee, Heui-Sam;Kim, Kee-Young;Kim, Mi-Ja;Kang, Pil-Don
    • International Journal of Industrial Entomology and Biomaterials
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    • v.24 no.2
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    • pp.63-68
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    • 2012
  • Osteoporosis is characterized by the reduced density of mineralized bone matrix. The loss of bone has been attributed to an imbalance between bone formation and bone resorption. The silkmoth is one of the famous traditional tonic medicines. Silkworm pupa was evaluated for its antiosteoporotic activity in an ovariectomized rat model of osteoporosis. The rats were ovariectomized at 6weeks of age and divided into 7 groups. All the groups were fed without calcium diet. The OVX rats were treated with water and silkworm powder for 6 weeks. In OVX rats, the body weight, feeding and water intake quantity did not show a significant change, but the silkworm pupa powder immediately before the eclosion of Yeonrokjam was significantly increased the bone mineral density in the femoral bone. The silkworm pupa powder increased the bone with increasing calcium in serum. These results also showed its protective action through promotion of bone formation. The silkworm pupa powder has a definite antiosteoporotic effect; similar to estrogen, it is especially effective for the prevention of bone fracture induced by estrogen deficiency. The silkworm pupa powder is a promising anti-osteoporotic agent that can prevent bone fractures in osteoporotic patients. The silkworm pupa powder does not show serious side effects because natural herbal medicine origin.

AN EXPERIMENTAL STUDY ON THE BONE REGENERATION OF TIBIAL BONE DEFECT (경골 이식의 골결손부 골재생에 대한 실험적 연구)

  • Kim, Su-Gwan;Yeo, Hwan-Ho;Kim, Soo-Min
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.20 no.4
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    • pp.275-278
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    • 1998
  • Recently, the clinical applications of the autogenous cancellous bone from the proximal tibial metaphysis show satisfactory results in the repair of maxillofacial bony defect or deformity. The proximal tibia has the potential to yield viable cancellous bone with a minimum of morbidity. The purpose of this study was to investigate the regeneration of a full thickness proximal tibial bone defect with covering or uncovering of cortical bone. The follow-up periods were 4, 8, and 12 weeks. Bone defect of right side was uncovered and left side was covered with cortical bone. In the experimental group (uncovered cortical bone) at 12 weeks, the inside of defect was filled to normal marrow tissue. The cortical bone defect was united of inner, outer callus at 4, 8 weeks in both study group. At 12 weeks, the cortical bone defect was remodeled and invaded by osteoclast (giant cell) in experimental group. In the experimental specimen at 12 weeks, the regenerating tissue of bone defect was not differ from the control group.

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High Glucose Inhibitory Effects on Bone Formation in UMR106 Cells

  • Kwon, Eun-Hee;Jung, In-Ok;Kim, Sung-Jin
    • Biomolecules & Therapeutics
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    • v.11 no.2
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    • pp.81-84
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    • 2003
  • Recently, diabetes has been found to be associated with osteoporosis. Specially in IDDM. In both type I and type II diabetes, glucose levels are elevated. Thus, a linkage between high glucose and osteoporosis can not be ruled out. In this study, an attempt has been made to observe the effect of high glucose on bone formation; osteoblast like UMR 106 cells were treated with high glucose (22 mM, 33 mM) for 1, 3 or 7 days. The high concentration of glucose inhibited markers. of bone formation activity such as alkaline phosphatase and collagen synthesis. In addition, reduction in the level of total cellular protein in response to high glucose was also observed. This study showed high glucose concentration could alter the bone metabolism leading to a defective bone formation and thus paving the linkage of such situation to diabetic complications.

Bone density around the fixture after function of implant molar prosthesis using CBCT (임플란트 보철 기능후 고정체 주변 콘빔CT 골밀도 평가)

  • Jung, Jae-Hyun;Hwang, In-Taik;Jung, Byung-Hyun;Kim, Jae-Duk;Kang, Dong-Wan
    • Imaging Science in Dentistry
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    • v.40 no.1
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    • pp.1-7
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    • 2010
  • Purpose : The purpose of this study was to examine the significance of increased bone density according to whether bone grafts were applied using demographic data with Cone Beam Computed Tomography (CBCT) and to compare the bone densities between before and after implant prosthesis using the Hounsfield index. Materials and Methods : Thirty-six randomly selected computed tomography (CT) scans were used for the analysis. The same sites were evaluated digitally using the Hounsfield scale with V-Implant $2.0^{TM}$, and the results were compared with maxillary posterior bone graft. Statistical data analysis was carried out to determine the correlation between the recorded Hounsfield unit (HU) of the bone graft and implant prosthesis using a Mann-Whitney U test and Wilcoxon Matched-pairs test. Results : The bone grafted maxillary posterior teeth showed an increase in the mean values from-157 HU to 387 HU, whereas non-grafted maxillary posterior teeth showed an increase from 62 HU to 342 HU. After implantation, the grafted and non-grafted groups showed significantly higher bone density than before implantation. However, the grafted group showed significantly more changes than the non-grafted group. Conclusion : Bone density measurements using CBCT might provide an objective assessment of the bone quality as well as the correlation between bone density (Hounsfield scale) and bone grafts in the maxillary molar area.

Combined Genotoxic Effects of Aflatoxin B1, Ochratoxin A and Zearalenone in Rat Bone Marrow and Blood Leukocytes

  • Tigran, Harutyunyan;Anna, Karapetyan;Galina, Hovhannisyan;Rouben, Aroutiounian
    • Korean Journal of Environmental Biology
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    • v.31 no.3
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    • pp.189-191
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    • 2013
  • Mycotoxins such as aflatoxin B1 (AFB1), ochratoxin A (OTA) and zearalenone (ZEA) are widespread contaminants of food and feedstuffs. It is very likely, that humans and animals are always exposed to mixtures of mycotoxins rather than to individual compounds. Therefore, risk assessments should consider mixture toxicity data. In the present study the combination of AFB1, OTA and ZEA was tested for genotoxicity in rat bone marrow and blood leukocytes after 15, 30 and 60 days treatment. The level of DNA damage was determined by the comet assay. The tail intensity and Olive tail moment in leukocytes and bone marrow cells were significantly higher than in controls. At the same time, the level of DNA damage in bone marrow cells was higher than in leukocytes. The data suggests that prolonged exposure to mycotoxins combination through food consumption can induce DNA damage contributing to the harmful effects in vivo.

CLINICAL STUDY ON TIBIAL BONE GRAFT (경골이식에 관한 임상 연구)

  • Kim, Sik;Kim, Su-Gwan;Kim, So-Young;Kim, Soo-Min;Park, In-Soon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.5
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    • pp.540-543
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    • 2000
  • The purpose of this retrospective study was to evaluate the treatment outcome of proximal tibial graft. Thirty-nine patients were grafted with proximal tibia for the repair of maxillofacial defect. Complications can be considered incidental and neglectable clinical significance. It is concluded that the proximal tibial metaphysis offers a promising alternative sources of cancellous bone for the repair of maxillofacial defect.

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The effect of irradiated cancellous human bone on exophytic bone formation in residual ridge of the beagle dog (방사선 조사 망상골이 외방형 골형성에 미치는 영향)

  • Chung, Mi-Hyun;Herr, Yeek;Kwon, Young-Hyuk;Park, Joon-Bong;Chung, Jong-Hyuk
    • Journal of Periodontal and Implant Science
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    • v.37 no.4
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    • pp.791-803
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    • 2007
  • The purpose of this study was to evaluate exophytically vertical bone formation in residual ridge of the beagle dog by the concept of guided bone regeneration with a titanium reinforced e-PTFE membrane combined with irradiated cancellous human bone. Twelve male beagle dogs(mean age 1.5 years and mean weight 12kg) were used for this study. The alveolar ridges after extraction of all mandibular premolars were surgically and horizontally removed. At 8 weeks after extractions, full-thickness flap was reflected and cortical bone was removed with round bur and copious irrigation. Rectangular parallelepiped(10mm in length, 5mm in width, and 4mm in height) bended with titanium-reinforced e-PTFE(TR e-PTFE) membrane was placed on the decorticated alveolar ridge, fixed with metal pins and covered with full-thickness flap and assigned as a control group. Test groups ere treated with TR e-PTFE membrane filled with irradiated cancellous human bone. Of twelve beagle dogs, four control dogs and four test dogs without membrane exposure to oral cavity were sacrificed at 8 and 16 weeks respectively. The surgical sites were dissected out, fixed in 4% buffered formaldehyde, dyed using a Villanueva staining technique, and processed for embedding in plastic resin. The cutting and grinding methods were routinely processed for histologic and histomophometric analyis of exophytic bone formation as well as statistical analysis. The results of this study were as follows: 1. Exophytic bone formation in the both of experimental groups was increased respectively after surgery from 23.40% at 8 weeks to 46.26% at 16 weeks in the control groups, from 40.23% at 8 weeks to 47.11% at 16 weeks in the test groups(p<0.05). 2. At 8 weeks after surgery, exophytic bone formation was made 40.23% in the test groups and 33.40% in the control groups. Exophytic bone formation was significantly made in the test group more than in the control group. At 16 weeks after surgery, exophytic bone formation was made 44.11% in the test groups and 46.26% in the control groups. Exophytic bone formation was made in the test groups more than in the control groups, but there was no statistically significant differences. 3. The membrane was fixed with metal pins to closely contact it to the bone surface. So, collapse and deviation of the membrane could be prevented and in growth of connective tissue also could be blocked from the periphery of the membrane. On the basis of these findings, wee suggest that intraoral experimental model for exophytic bone formation may be effective to evaluate the effect of bone graft material. And it indicates that combined use of membrane and ICB graft material is more effective than use of membrane only for exophytic bone formation.