• 대한치과교정학회지
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• 제20권3호
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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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• 제31권2호
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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.

• 약학회지
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• 제59권2호
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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.

• 대한본초학회지
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• 제35권3호
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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.

• 대한치과교정학회지
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• 제30권6호
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• pp.713-721
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• 2000

골세포는 골대사에 영향을 미치는 다양한 성장인자와 싸이토카인을 생성하여 골 기질로 유리시킨다. 이 연구는 쥐의 장골 세포 배양 모델에서 recombinant human IL-$1\beta$가 $PGE_2$ 합성과 plasminogen activator의 활성 조절을 통한 골 흡수 유도 기전의 일단을 구명하고, 이와 동시에 TGF-$\beta$에 의한 골흡수 억제 기전을 해명하는데 그 목적이 있다. 쥐의 장골 세포를 배양하여 통법의 골모세포 phenotype을 발현하는 세포를 분리하고 세포 배양능, alkaline phosphatase assay, PG assay, 골흡수능 측정들을 시행하여 다음의 결과를 얻었다. 1. IL-$1\beta$는 쥐의 골모세포의 증식, $PGE_2$ 생성 및 palsmonogen activator의 활성을 촉진하였다. 2. IL-$1\beta$는 쥐의 골모세포에서의 alkaline phosphatase 활성을 감소시켰다. 3. rhIL-$1\beta$는 골 흡수를 촉진시켰다. 4. TGF-$\beta$는 쥐의 장골 세포에서 골의 흡수를 억제하였으며, Vitamin $D_3$에 의하여 유도된 골 흡수를 억제하였다. 이상의 연구 결과는 IL-$1\beta$에 의한 골 파괴의 병인과 관련하여 골 세포 대사의 병리학적 조절에 있어서의 IL-$1\beta$의 역할을 지지하며, 이와 동시에 골 흡수 억제에 있어서의 TGF-$\beta$의 역할을 확인시켜주는 것으로 생각된다.

• 약학회지
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• 제50권3호
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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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• 제16권6호
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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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• 제40권4호
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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.

• 한국축산식품학회지
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• 제32권2호
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• pp.234-240
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• 2012

본 연구에서는 난소 제거로 인위적으로 골다공증이 유발된 흰쥐를 대상으로 돼지껍질에서 추출한 젤라틴과 저분자 젤라틴 효소분해물 급여가 골밀도에 미치는 영향을 조사하였다. 실험군의 구성은 10주령의 암컷 총 6군으로 난소 적출을 시행 하지 않은 일반 대조군과 난소 적출한 대조군은 일반식이를 급여하였으며, 난소 적출한 실험쥐에 3kDa 이하의 저분자 젤라틴 효소분해물을 0.1, 0.8% 첨가하고, 고분자 젤라틴을 0.1과 0.8% 첨가하여 급여한 후 그 효과를 비교하였다. 체중 증가량은 GH0.1, GH0.8 및 G0.8 급여구에서 NC와 OC에 비해 유의적으로 증가하였으며 특히 GH0.1과 GH0.8처리군은 사료섭취량이 NC와 OC에 비해 증가하였으나 사료효율은 유의적인 차이를 보이지 않았다. 대퇴골의 골밀도는 GH0.8처리군이 OC군에 비해 높았으나(p<0.05) NC의 수준에는 미치지 못하였다. 혈중 총 콜레스테롤 함량은 처리군간의 유의적인 차이를 보이지 않았으나 젤라틴 급여군과 GH 급여군의 HDL-C은 OC군에 비해 유의적인 증가를 나타내었다. 혈중 alkaline phosphatase(ALP)와 osteocalcin은 각각 GH0.1과 GH0.8에서 유의적인 감소를 나타내었다(p<0.05). 간질환의 지표인 혈중 GOT와 GPT도 모든 처리구에서 OC에 비해 유의적으로 감소하였다. 따라서 본 연구결과 돼지껍질에서 분리한 저분자 젤라틴 효소분해물은 골밀도를 증진시키고 폐경기 여성의 골건강에 도움을 줄 수 있는 수용성 기능성 소재로 이용 가능성이 있을 것으로 기대되지만 젤라틴 급여구의 높은 단백질 함량으로 젤라틴 효소분해물의 효과가 미미하여 비교시 골밀도 증진 효과의 유의적인 차이가 없어 추후 적정농도 설정에 관한 연구가 추가되어야 할 것으로 판단된다.

• 한국식품과학회지
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• 제34권4호
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• pp.710-718
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• 2002

콩과 식물인 갈근에는 genistein과 daidzein이 함유된 것으로 알려졌으므로 본 연구는 갈근(PR), 갈화(PF) 및 어린순인 갈용(PL)에 함유된 phytoestrogen의 함량을 HPLC법으로 정량 분석하였다. 동시에 phytoestrogen의 골다공증 치료제에 대한 효능 검색의 일환으로 조골세포의 증식작용(MTT법 및 ALP분석)과 피골세포의 활성(TRAP법)을 측정하였고 난소절제 흰쥐에 PR 1 g/kg/day(PR-1) 및 PR 5 g/kg/day(PR-5)을 9주 동안 투여한 후 혈액분석, 혈장 Alkaline phospatase(ALP), 칼슘, 무기성 인산염, 총콜레스테롤, LDL- 및 HDL-콜레스테롤을 측정하였고 적출된 경골 및 요추골의 소주골면적을 측정하였다. PR과 PF의 총 daidzein의 함량은 $10436{\pm}2144\;mg/kg$와 $1003{\pm}206\;mg/kg$이었고 genistein과 formononetin은 PR에만 존재하고 PF 및 PL에는 함유되어 있지 않았다. 인간 유사 조골 세포주인 Saos-2에 PR은 대조군의 158% 정도(5 mg/mL)의 세포증식효과와 ALP 활성을 증가시켰으나 전처리한 PR, PF 및 PL의 세포증식효과는 없었고 PL만이 ALP 활성을 증가시켰다. 파골세포의 증식억제실험에서 genistein의 $IC_{50}$는 $1.57{\times}10^{-4}\;mg/mL$ $(5.81{\times}10^{-7}\;M)$이었고, daidzein과 PR은 효과가 없었다. 난소절제 흰쥐에 대한 in vivo 실험에서 대조군이 sham군보다 난소적출 1주 후부터 체중의 증가가 급격하게 나타났으나 PR의 투여로 둔화되었다. PR 투약에 의한 자궁의 무게는 PR-5군은 대조군에 비해 증가되었고(p<0.05), PR-1군은 대조군과 유의성이 없었다. 혈장 ALP의 활성은 주령의 증가에 EK라 감소하는 경향을 보였고, HDL-콜레스테롤의 농도는 모든 군에서 주령에 따라 감소되었으나(p<0.01), PR-5군의 LDL-콜레스테롤의 농도는 대조군에 비해 감소되었다(p<0.01). 대조군에 비해 sham군의 경골 및 요추골의 면적은 증가되었고(p<0.01), PR 투여군(PR-1 및 PR-5)도 sham보다 적으나 대조군에 비해 소주골 면적이 증가되었다(각 p<0.01). 특히 고용량의 PR 투여는 PR의 골다공증 치료효과가 우수함을 증명하였으며(p<0.01), PL과 PF는 효능이 미비하나 PR은 골다공증의 예방 및 치료제로는 상당히 우수한 한약재임이 확인되었다.