• The korean journal of orthodontics
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• v.20 no.3 s.32
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• pp.499-517
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• 1990

Electrical stimulation among several factors that influence bone remodeling has been studied by many investigators with great enthusiasm in orthodontic field. The action mechanisms of Pulsed Electromagnetic Field (PEMF) are different from those of the conventional electrode application method in that PEMF induces endogenous current in the living tissues. PEMF is known to have the healing effect in nonunion of bone and osteoporosis. It is widely used in orthopaedic scopes and the possibility of using the method in clinical orthodontics Is also conceivable. But the exact mechanisms by which the PEMF exerts its effects are not clearly understood. Therefore, the author wanted to see the effect of PEMF on five groups of rat calvarial cells obtained by sequential enzyme digestion method, and observed the changes in enzyme activation, collagen synthesis and $^3H-thymidine$ incorporation. The results were as follows: 1. Under the effect of PEMF, there were no changes in the alkaline phosphatase activity in five groups of cell populations. 2. Both the PEMF group and the PTH with PEMF group shelved no changes in acid phosphatase activities and there were no differences between two experimental groups. 3. Under the effect of PEMF, there was significant increase of collagen synthesis in the group V cell population. 4. Under the effect of PEMF, there were significant increases of $^3H-thymidine$ incorporation in the group IV and V cell populations.

• Journal of Periodontal and Implant Science
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• v.31 no.2
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• pp.389-400
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• 2001

Previous studies have demonstrated an increase in bone mass and density with the use of bisphosphonate in osteoporosis. This agent acts as an inhibitor of osteoclastic activity, and results in increase of net osteoblastic activity. Currently, it has been reported that bisphosphonate has direct effect on osteoblast. This study was designed to evaluate the effect of alendronate on bone regeneration in defect of rat calvaria. The animals used for these experiments were 48 male rats, over 6-8 weeks old. They were divided into three groups according to the dose of alendronate($MK-217^{(R)}$, Merck, USA) administered. After the calvarial defects were surgically created, the rats received a peritoneal alendronate(0.25mg/kg) in group I, a peritoneal alendronate(1.25mg/kg) in group II, and a peritoneal normal saline injection in the control group. Three and six weeks later, blood was sampled and evaluated for alkaline phosphatase activity. The animals were sacrificed for histological observation and histometric analysis of the level of bone formation. The alkaline phosphatase activity was similar in three groups at 3 weeks of experiment. The activity at 6 weeks increased more than twice, compared to 3 weeks, and was slightly higher in group I than the other two groups. In histological observation, all the groups at 3 weeks, osteoblast rimming and new bone formation were observed along the defect margin. At 6 weeks, the defect was almost closed with new and more mature bone, but new bone is thinner than original bone in the central portion of defect. In histometric analysis, group I and II at 3 weeks showed significantly greater new bone formation than the control, and all the groups at 6 weeks showed similar amount of bone formation. These result suggest that alendronate administration in the dose of 0.25mg/kg and 1.25mg/kg promote osseous regeneration.

• YAKHAK HOEJI
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• v.59 no.2
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• pp.59-65
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• 2015

KR-67500, trans-4-(2-(4-methyl-1,1-dioxido-6-(2,4,6-trichlorophenyl)-1,2,6-thiadiazinan-2-yl)acetamido)adamantane-1-carboxamide, is a novel $11{\beta}$-HSD1 inhibitor with its therapeutic effects of its anti-diabetic, anti-adipogenic and anti-osteoporotic activity. This study was performed to evaluate in vitro and in vivo pharmacokinetic properties of KR-67500 as a new drug candidate. KR-67500 was stable and highly bound to proteins in rat plasma. The microsomal stabilities of KR-67500 in human and rat liver were high. The inhibitory effect of KR-67500 for five cytochrome P450 enzymes was low. Preclinical pharmacokinetic studies have been carried out with intravenous or oral administrations of KR-67500 (10 mg/kg) to male rats and monkey. KR-67500 showed low clearance (0.68 l/h/kg) and high oral bioavailability (102%) in male rats. These results suggest that KR-67500 has good drug-like pharmacokinetic properties with a low first-pass effect and high bioavailability for an oral therapeutic agent of diabetes and osteoporosis.

• The Korea Journal of Herbology
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• v.35 no.3
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• pp.1-8
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• 2020

Objectives : In this study, we examined the estrogenic activities and anti-osteo clastogenesis effects of PCE17, a mixture of PE (an extract of Puerariae Flos), and CE (an extract of Citri Unshius Pericarpium). Methods : The estrogenic effect of PCE17, PE and CE were examined by ER-β/ERE reporter gene assay and proliferation assay in 293 T and MCF-7 cells. The expression of estrogen-responsive gene and protein were checked by Real Time-PCR (RT-PCR) and Western blotting in MCF-7 cells. Inhibitory effect of PCE17, PE and CE on RANKL-induced osteoclast differentiation were evaluated by TRAP staining and RT-PCR in primary osteoclast precursors from rat bone marrow cells. Results : PCE17 and PE bind to ERs (estrogen receptors) and show estrogenic activities in 293T cells. They also stimulated the proliferation of MCF-7 cells and increased the expression of ER response gene, pS2. Tectorigenin, an active ingredient of PE, shows similar estrogenic activities in MCF-7 cells. PCE17 and CE inhibited RANKL-induced osteoclastogenesis in rat primary osteoclast precursor cells and down-regulated the osteoclast-specific genes of Nfatc1, Ctsk, and Acp5. Conclusions : In conclusion, PCE17 may have therapeutic potential in cases of menopause and osteoporosis.

• The korean journal of orthodontics
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• v.30 no.6 s.83
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• pp.713-721
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• 2000

Bone cells produce multiple growth factors and cytokines that have effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-$\beta$(TGF-$\beta$) or interleukin-$1\beta$(rhIL-$1\beta$) and bone cells in a rat long bone culture model. IL-$1\beta$ regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-$1\beta$ stimulated cellular proliferation as well as the synthesis of prostaglandin $E_2$ and Plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-$\beta$ is present in the bone matrix and potentially released during bone resorption. TGF-$\beta$ reduced basal bone resorption and inhibited vitamin $D_3[1,25(OH)_2D_3]$-induced bone resorption in rat long bone cells. These results support the role of IL-$1\beta$ in the pathological modulation of bone cell metabolism, with regard to implication in the Pathogenesis of osteoporosis by IL-$1\beta$, and that TGF-$\beta$ positively inhibits the bone resorption.

• YAKHAK HOEJI
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• v.50 no.3
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• pp.160-165
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• 2006

Germanium is found in a range of minerals and ores and is present in foods including beans, tomato juice, oysters, tuna and garlic. Germanium is a non-metallic element, which can exist in valence states of 2 and 4. Clinical trials and use in private practices for more than a decade have demonstrated organic germanium's efficacy in treating serious disease including cancer, arthritis and senile osteoporosis. But it was rarely reported that inorganic germanium has biological properties. STB-BM contains mineral complex, rare earth elements and a little amount of Inorganic germanium. The experiment was carried out the anti-obesity effect. To investigate anti-obesity effect of STB-BM, we measured the effect of body weight, fat weight (subcutaneous fat, epididymal fat, visceral fat, kidney fat and total fat) and serum biochemical level in rats fed high fat diets. STB-BM 35 mg/kg suppressed the increasing ratio of body weight, epididymal fat weight, visceral fat weight, total fat weight, triglyceride and LDL-cholesterol (p<0.05).

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2161-2166
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• 2015

Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human $ER{\alpha}$, mouse $ER{\alpha}$, rat $ER{\alpha}$, dog $ER{\alpha}$, and cat $ER{\alpha}$ are above 90%, but structures of $ER{\alpha}$ may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to $17{\beta}-estradiol$ (E2), which is a natural ligand of both $ER{\alpha}$ and $ER{\beta}$. The RBA of the estrogen species are as following: diethyl stilbestrol (DES) > hexestrol > dienestrol > $17{\beta}-estradiol$ (E2) > 17- estradiol > moxestrol > estriol (E3) >4-OH estradiol > estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies.

• Journal of Nutrition and Health
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• v.40 no.4
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• pp.320-326
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• 2007

An important related question is whether arginine has influence bone metabolism. The effect of arginine supplements on bone markers and related hormones were studied in young female Sprague-Dawley rats fed either an arginine supplemented diet or control diet. Twenty four rats (body weight 83${\pm}$5 g) were randomly assigned to one of two groups, consuming casein or casein with supplemented arginine diet. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. And bone resorption rate was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Serum osteocalcin, growth hormone, estrogen, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH) and calcitonin were analyzed using radioimmunoassay kits. The weight gain and mean food intake were not affected regardless of diets. The rats fed arginine-supplemented diet had not significantly different in ALP, osteocalcin, crosslinks value, PTH, estradiol, and IGF-1 compared to those fed casein diet group. The arginine-supplemented group had significantly higher growth hormone and calcitonin than casein group. This study suggests that arginine is beneficial for bone formation in growing female rats. Therefore exposure to diet which rich in arginine early in life may have benefits for bone formation and osteoporosis prevention.

• Food Science of Animal Resources
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• v.32 no.2
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• pp.234-240
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• 2012

This study was conducted to examine the effects of low molecular weight gelatin hydrolysates (GH, less than 3kDa), extracted from pig skin collagen on the bone metabolism of ovariectomized (OVX) rats. The rats in the experimental groups were randomly segregated into six different treatment groups such as 1) NC, the normal rat fed AIN 93 diet (basal diet) only; 2) OC, the OVX rat fed the basal diet only; 3) GH 0.1, the OVX rat fed the basal diet with 0.1% GH; 4) GH 0.8, the OVX rat fed the basal diet with 0.8% GH; 5) G 0.1, the OVX rat fed the basal diet with 0.1% gelatin; 6) G 0.8, the OVX rat fed the basal diet with 0.8% gelatin. Body weight gain in the GH 0.1, GH 0.8, and G 0.8 was significantly higher than those in the NC and OC. Feed intake of the GH 0.1 and GH 0.8 was higher than that of the NC and OC, while no significant difference was found in feed efficiency ratio (FER). BMD of the GH 0.8 was higher than that of the OC. However, gelatin hydrolysates and gelatin resulted in higher BMC level compare to the OC. Serum HDL-cholesterol of rat fed GH and gelatin was higher than that of OC (p<0.05). LDL-C of the GH 0.1 and the GH 0.8 tended to be less than that of OC. Serum alkaline phosphatase (ALP) of the GH 0.1 was lower than that of the OC. The serum of GH 0.8 showed lower osteocalcin value than the OC (p<0.05). In addition, GOT and GPT levels significantly decreased in all treatment groups. These results indicated that gelatin hydrolysates from pig skin gelatin hydrolysates enhanced BMD and serum biochemical parameters related to bone metabolism. Therefore, the gelatin hydrolysates could be used as a beneficial material to improve bone health.

• Korean Journal of Food Science and Technology
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• v.34 no.4
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• pp.710-718
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• 2002

It is reported that Pueraria Radix contains phtoestrogens whereas flower, and bud of Pueraria lobata Ohwi were not known. In the present study, we determined the amount of phytoestrogen in each portion of P. lobata Ohwi and carried out therapeutic effects of osteoporosis. The amounts of genistein, daidzein, and formononetin in Pueraria Radix (PR), Pueraria Flos (PF), and young Pueratia Folium (PL) were quantitated using a HPLC system. Proliferation of osteoblast and growth inhibitory effect on osteoclast were measured in order to screen their effects on osteoporosis. Proliferation of osteoblast-like cells (Saos-2) was analyzed by both MTT methods and alkaline phosphatase (ALP) assays. Growth inhibitory effect on osteoclast was also detected as Tartrate resistant acid phosphatase (TRAP) assay. Ovariectomized rat as an in vivo animal model was selected and administrations of PR were 1 g/kg/day (PR-1) and 5 g/kg/day (PR-5) for 9 weeks, respectively. Trabecular bone areas (TBAs) of tibia and lumbar were analyzed usibg histomorphological methods. Results show that PR contains the highest level of daidzein ($10435{\pm}2143\;mg/kg$ of dried herb) and stimulated ALP activity, approximately 160% of the control. Growth inhibitory effect on osteoclast by both PR and daidzein were almost identical with control although $IC_{50}$ of genistein was $5.81{\times}10^{-7}$ M. Increases in body weight of OVX rats were suppressed by administration of PR but wet weights of uterus in PR-5 group were increased (p<0.05). Plasma ALP and HDL-cholesterol levels were decreased following ages (p<0.01), and LDL-cholesterol level was also decreased in PR-5 group at 20 week of age (p<0.01). TBAs of tibia and lumbar in PR-1 and PR-5 groups were higher than those of the control although the values were less than those of the sham group (each p<0.01) In conclusion, administrations of PR prevented loss of TBAs of tibia and lumber in OVX rats, while PL and PF did not (p<0.01).