• The korean journal of orthodontics
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• v.34 no.6 s.107
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• pp.526-536
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• 2004

This study was undertaken to determine the effect of a 2.2mg/Kg/day intraoral administration of NaF on the amount of root resorption and osteoclastic activity during or after a rapid maxillary expansion procedure. Ten puerile female dogs were divided into two groups: a control group and a NaF-treated group. A fixed type maxillary expansion device was delivered to all dogs. The appliance was activated twice daily throughout a 20-day period, causing a 5-mm expansion of maxillary bone. After the expansion procedure, the animals were sacrificed at days 0, 15, 30, 45, and 60 of the retention period. The buccal surface of the root of each maxillary canine was examined by means of a surface electron microscope (SEM). Using SEM, web-like resorption lacunae were observed on the bone or the tooth surface at the site of osteoclastic activity; these observations were verified by histological methods. No peculiar resorption lacunae were found in the apical tip of the roots of either the control group or the NaF-treated group animals. The NaF-treated retention group was found to have less resorption lacunae formation on day 45 and day 60. The preventative effect of NaF on resorption lacunae formation on the surface of the bone covering the anchor tooth was confirmed. Larger areas of resorption lacunae were found on the surface of the bone covering the canines in the control group animals, as compared to those of the NaF-treated group, especially on day 30 and day 60. Using SEM, the present study revealed a difference between the control group and the NaF-treated group in the prevalence and the size of the resorption lacunae formation on the cemental root surface. The preventative effect of NaF on bone resorption was confirmed. Further studies concerned with the optimum concentration of NaF that has an effect in vivo are necessary.

• Journal of Cancer Prevention
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• v.21 no.2
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• pp.88-94
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• 2016

Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

• Journal of Periodontal and Implant Science
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• v.24 no.2
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• pp.321-339
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• 1994

The cytokines released by osteoblasts induce bone resorption via the differentiation of osteoclast precursors. In this process, $interleukin-1{\beta}$($IL-1{\beta}$)-induced bone resorption is mediated by granulocyte macrophage-colony stimulation factor(GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor ${\alpha}$($TNF-{\alpha}$) released from osteoblasts. Since these cytokines (GM-CSF, IL-6, $TNF-{\alpha}$) are produced by not only osteoblasts but also monocytes, and interleukin-10(I1-10) inhibits the secretion of these cytokines from monocytes, it may be speculated that IL 10 could modulate the production of GM-CSF, IL-6, and $TNF-{\alpha}$ by osteoblasts, then control $IL-1{\beta}-induced$ bone resorption. Therefore, the aims of the present study were to examine the effects of IL-10 on bone resorption. The sixten or seventeen-day pregnant ICR mice were injected with $^{45}Ca$ and sacrificed one day after injection. Then fetal mouse calvaria prelabeled with $^{45}Ca$ were dissected out. In order to confirm the degree of bone resorption, mouse calvaria were treated with Lipopolysaccharide(LPS), $TNF-{\alpha}$, $IL-1{\alpha}$, IL-8, $IL-1{\beta}$, and $IL-1{\alpha}$, Then, IL-10 and $interferon-{\gamma}$ ($IFN-{\gamma}$) were added to calvarial medium, in an attempt to evaluate the effect of $IL-1{\beta}-induced$ bone resorption. In addition, osteoclasts formation in bone marrow cell cultures, and the concentration of IL-6, $TNF-{\alpha}$, and GM-CSF produced from mouse calvarial cells were investigated in response to $IL-1{\beta}$ alone and simultaneously adding f $IL-1{\beta}$ and IL-10. The degree of bone resorption was expressed as the ratio of $^{45}Ca$ release(the treated/the control). The osteoclasts in bone marrow cultures were indentified by tartrate resistant acid phosphatase(TRAP) stain and the concentration of the cytokines was quantified using enzyme linked immunosorbent method. As results of these studies, bone resorption was induced by LPS(1 ng/ml ; the ratio of $^{45}Ca$ release, $1.14{\pm}0.07$). Also $IL-1{\beta}$(1 ng/ml), $IL-1{\alpha}$(1 ng/ml), and $TNF-{\alpha}$(1 ng/ml) resulted in bone resorption(the rations of $^{45}Ca$ release, $1.61{\pm}0.26$, $1.77{\pm}0.03$, $1.20{\pm}0.15$ respectively), but IL-8 did not(the ratio of $^{45}Ca$ release, $0.93{\pm}0.21$). The ratios of $^{45}Ca$ release in response to IL-10(400 ng/ml) and $IFN-{\gamma}$(100 ng/ml) were $1.24{\pm}0.12$ and $1.08{\pm}0.04$ respectively, hence these cytokines inhibited $IL-1{\beta}$(1 ng/ml)-induced bone resorption(the ratio of $^{45}Ca$ release $1.65{\pm}0.24$). While $IL-1{\beta}$(1 ng/ml) increased the number of TRAP positive multinulcleated cells in bone marrow cultures($20{\pm}11$), simultaneously adding $IL-1{\beta}$(1 ng/ml) and IL-10(400 ng/ml) decreased the number of these cells($2{\pm}2$). Nevertheless, IL-10(400 ng/ml) did not affect the IL-6, GM-CSF, and $TNF-{\alpha}$ secretion from $IL-1{\beta}$(1 ng/ml)-activated mouse calvarial cells. From the above results, it may be suggested that IL-10 inhibites $IL-1{\beta}-induced$ osteoclast differntiation and bone resorption. However, the inhibitory effect of IL-10 on the osteoclast formation seems to be mediated not by the reduction of IL-6, GM-CSF, and $TNF-{\alpha}$ production, but by other mechanisms.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.34 no.6
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• pp.398-403
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• 2012

Purpose: Mandible resection and discontinuity defect created lead to aesthetic and functional problems. The iliac crest bone graft exhibits relative ease for bone harvesting, possibility of two team approach, ability to close the wound primarily, large amount of corticocancellous bone and relatively few complications. Whereas the use of free vascularized flaps has donor site morbidity and worse-fitting bone contour, the use of nonvascularized iliac bone graft has advantages in the operation time and patients' recovery time. So, nonvascularized iliac bone graft could be an attractive option. Methods: Twenty-one patients (M:F=1:1.1) underwent iliac crest bone harvesting for reconstruction of mandibular discontinuity defect (mean length : $61.6{\pm}17.8$ mm), from May 2005 to October 2011 at the Department of Oral and Maxillofacial Surgery in Kyungpook National University. The average age was $44.1{\pm}16.4$ years and the mean follow up periods was $28.2{\pm}22.7$ months. Bone resorption rate, according to age, sex, primary lesion, location and distance of defect, type of fixation plate, time of graft and pre-operative radiation therapy, were measured in each patient. Results: The mean bone resorption rate was $16.1{\pm}9.0%$. Bone resorption rate was significantly increased in mandibular defect that is over 6 cm in size (P=0.015, P<0.05) and the cases treated pre-operative radiation therapy (P=0.017, P<0.05). All was successfully fixed and maintained for the long-term follow-up. There were a few donor site complications and almost all patients were shown favorable outcome without severe bone resorption in this study. Conclusion: The nonvascularized iliac bone graft seems to be a reasonably reliable treatment option for reconstruction of mandibular discontinuity defects.

• The korean journal of orthodontics
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• v.46 no.3
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• pp.155-162
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• 2016

Objective: The aim of this study was to investigate whether labial tooth inclination and alveolar bone loss affect the moment per unit of force ($M_t/F$) in controlled tipping and consequent stresses on the periodontal ligament (PDL). Methods: Three-dimensional models (n = 20) of maxillary central incisors were created with different labial inclinations ($5^{\circ}$, $10^{\circ}$, $15^{\circ}$, and $20^{\circ}$) and different amounts of alveolar bone loss (0, 2, 4, and 6 mm). The $M_t/F$ necessary for controlled tipping ($M_t/F_{cont}$) and the principal stresses on the PDL were calculated for each model separately in a finite element analysis. Results: As labial inclination increased, $M_t/F_{cont}$ and the length of the moment arm decreased. In contrast, increased alveolar bone loss caused increases in $M_t/F_{cont}$ and the length of the moment arm. When $M_t/F$ was near $M_t/F_{cont}$, increases in Mt/F caused compressive stresses to move from a predominantly labial apical region to a palatal apical position, and tensile stresses in the labial area moved from a cervical position to a mid-root position. Although controlled tipping was applied to the incisors, increases in alveolar bone loss and labial tooth inclination caused increases in maximum compressive and tensile stresses at the root apices. Conclusions: Increases in alveolar bone loss and labial tooth inclination caused increases in stresses that might cause root resorption at the root apex, despite the application of controlled tipping to the incisors.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.431-436
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• 2013

Bone homeostasis is maintained by co-ordination of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between osteoclasts and osteoblasts leads to many bone diseases such as osteoporosis, rheumatoid arthritis. Taxillus chinensis is a herb that has been widely used to improve bone health. However, the effect and mechanism of Taxillus chinensis extract on osteoclast differentiation and bone resportion has been unknown. Thus, We investigated the effect of Taxillus chinensis on expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation and bone resorption. Also, the action of Taxillus chinensis on mechanisms relating to osteoclast differentiation was studied. In this results, we identified that Taxillus chinensis significantly inhibited RANKL-induced osteoclast differentiation and bone resportion. Moreover, Taxillus chinensis was suppressed the activation of NF-${\kappa}B$ in bone marrow macrophage treated RANKL and M-CSF. Taxillus chinensis was down-regulated the mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP). The cell adhesion-related molecules such as integrin ${\alpha}v$ and integrin ${\beta}3$, and the filamentous actin (F-actin) rings of mature osteoclasts-related molecules such as dendritic cell-specific transmembrane preotein (DC-STAMP) and cathepsin K are also suppressed. Taken together, these results indicated that Taxillus chinensis will be a good candidate to treat osteoclast-mediated bone diseases.

• The Korea Journal of Herbology
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• v.38 no.5
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• pp.9-19
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• 2023

Objectives : Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density and increased risk of fractures. Bisphosphonates and selective estrogen receptors, which are bone resorption inhibitors that are currently widely used as osteoporosis treatments, show serious side effects when administered for a long time. Research on bone resorption inhibitors that complement the problems of existing treatments is needed. The purpose of this study was to investigate the effect of inhibiting osteoclast differentiation and activity on the tuberous root of Ampelopsis japonica (Thunb.) Makino (AM). Methods : After extracting AM using distilled water and ethanol, the inhibitory effects of the two solvents on osteoclast differentiation were compared using the RANKL-induced in vitro experimental model and the TRAP assay kit. The impact of AM on bone resorption was investigated through the pit formation assay, and its effect on F-actin formation was assessed through fluorescent staining. Additionally, protein and mRNA expression levels of osteoclast differentiation markers (NFATc1, c-Fos, TRAP and ATP6v0d2) and resorption markers (MMP-9, CTK, and CA2) were analyzed via western blot and RT-PCR. Results : AM treatment significantly decreased the number of TRAP-positive cells and pit formation area. Furthermore, AM suppressed both the protein and mRNA expression of NFATc1 and c-Fos, key transcription factors involved in osteoclast differentiation and it downregulated the expression of osteoclast-associated genes such as TRAP, CTK, MMP-9, CA2, and ATP6v0d2. Conclusions : These results suggest that AM can inhibit bone resorption and osteoclast differentiation, indicating its potential for use in the treatment and prevention of osteoporosis.

• The korean journal of orthodontics
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• v.30 no.6 s.83
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• pp.723-730
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• 2000

Orthodontic tooth movement requires remodelling of periodontal tissues, especially alveolar bone. Fluoride is known to be a potent inhibitor of osteoclastic bone resorption. The purpose of this study was to examine the effects of a consumption of fluoride on osteoclast numbers appearing on the pressure side of alveolar bones at experimental tooth movement. 40 male rats were exposed to 0, 10, 25 mg/kg/day of sodium fluoride(NaF) in their drinking water for up to 60 days. Orthodontic appliance were activated to mesially tip maxillary first molar with 50-70g. The rats were sacrificed at 1, 2, 4 days after initial activation. The number of osteoclast was counted in a $450\times700\;{\mu}m^2$ area interradicular septum on the pressure side of the maxillary first molar. The results were as fellows, 1. There was significantly different osteoclast number between control group and 25 mg/kg/day group at all measured time. (p<0.05) 2. There was significantly different active bone-resorption area between control group and 25 mg/kg/day group except at 96 hours post activation. (p<0.05) 3. There was slight reduction of active bone- resorption area in control group from 48 hours to 96 hours but in both 10 mg/kg/day group and 25 mg/kg/day group a slight increase was observed from 48 hours to 96 hours.

• Korean Journal of Acupuncture
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• v.38 no.3
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• pp.140-150
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• 2021

Objectives : The increase of osteoclasts could cause osteoporosis and bone-related diseases. Also, the inhibition of osteoclast differentiation is important in treating bone-related diseases. Traditionally, Psoraleae Semen has been used for geriatric diseases, aging and musculoskeletal diseases. The purpose of this study is to investigate the effect of Psoraleae Semen ethanol extract (PS) on osteoclast differentiation and its function. Methods : To confirm the effect of PS on osteoclastogenesis and bone resorption activity, various levels of concentrations of PS (5, 10, 20 and 40 ㎍/ml) were tested on RAW 264.7 cells cultured with RANKL. We measured tartarate-resistant acid phosphatase (TRAP)-positive cells, TRAP activity, pit formation and F-actin ring formation. The expressions of nuclear factor of activated T-cells (NFATc1) and c-Fos were confirmed through western blot and reverse transcription- polymerase chain reaction (RT-PCR). Also, the expression of bone resorption and fusion-related genes in osteoclast was confirmed by RT-PCR. Results : PS decreased the number of TRAP-positive cells and the TRAP activity. In addition, PS significantly inhibited the formation of pit and F-actin ring. Furthermore, PS decreased the expression of osteoclast related genes. Conclusions : PS inhibits osteoclast differentiation and bone resorption ability through inhibition of the expression of osteoclast-related genes. This indicates that PS may be a potential therapeutic agent to osteoporosis by suppressing osteoclastogenesis.

• Journal of Periodontal and Implant Science
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• v.29 no.3
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• pp.507-519
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• 1999

The ultimate objective of periodontal treatment is to stop disease progression and to regenerate destroyed periodontal tissues and thereby regain normal function. Growth factors are naturally found polypetides which stimulate many cellular activities pertaining to wound healing by acting as signal molecule in controlling cell movement, proliferation, and matrix production. Platelet derived growth factor (PDGF) is 28,000-35,000 Da molecular weight dimeric protein with 2 long positively charged polypeptide chains connected by sulfide bonds. The purpose of this study is to evaluate histologically the initial guided tissue regeneration in a periodontal defect f a beagle dog treated with a biodegradable membrane formed with polylactic acid (poly-L-lactic acid) and polyglycolic acid loaded with 200ng/$cm^2$ platelet derived growth factor. 2 beagle dogs were used in he experiment. $5mm{\times}6mm$ alveolar bone defect was formed in upper and lower canines and third premolars and a reference notch was placed. PDGF-BB non-containing membrane was used as control. Each defect was randomly assigned to the test roup or the control group. The dogs were sacrificed 3 weeks after membrane placement. Toluidine blue and multiple staining was done for histological analysis. In the 3 week specimen in the control group, no new one formation could be seen. Small amount f bone resorption below the notch could be seen. In the notch, loose connective tissue with infiltration of inflammatory cells could be seen. Also thin discontinuous new cementum could be seen and the membrane still retained its structure. Where PDGF-BB containing membrane was used, new bone formation could be seen in the notch at weeks and also continuous thin cementum could be seen. PDL cells were observed between new bone and new cementum and some were attached to bone and cementum. These results suggest that new bone and cementum formation seen when PDGF-BB loaded membrane was used was due to inhibition of downgrowth of epithelial cells and also due to continuous release of the growth factor. Further study on the resorption characteristics of the membrane nd the release characteristics of the PDGF-BB is necessary. Also, development of a membrane easier to use clinically is necessary.