Polygoni Multiflori Radix (PMR), a dried root tuber of Polygonum multiflorum Thunberg with bioactivities in bone metabolism is one of the most famous tonic traditional medicines. To observe in vivo anti-osteoporotic efficacy of PMR extracts, we orally administered once a day for 28 days (Qd ${\times}$ 28) to bilateral ovariectomized (OVX)-induced osteoporosis ddY mice after 1 week of recovery periods at 125, 250 and 500 mg/kg (of body weight). A positive control drug, Alendronate (FOSA) 10 mg/kg-dosing group was added. As results of OVX-induced osteoporotic process, estrogen-deficient osteoporotic changes were also dramatically decreased in all PMR extracts-dosing groups. Especially middle dosage of PMR extracts, 250 mg/kg constantly and significantly (p < 0.01 or p < 0.05) inhibited the loss of bone strength and bone quality. Based on the results, it was concluded that PMR extracts (125, 250 or 500 mg/kg; orally dosing) has relatively good favorable effect to prevention and/or treatment of OVX-induced osteoporosis. Therefore, although the efficacy was slighter than that of Alendronate on the inhibition of bone loss, it is expected that PMR extracts will be promising as a new anti-osteoporotic agents for prevent the fracture induced in osteoporotic patients because natural herbal medicine origin PMR extracts will be dose not show serious side effects especially the problem in upper alimentary irritation by bisphosphonate and hypercalcaemia of parathyroid hormone analogs.
KIM , SEYL;KANG, JIN-SEOK;JANG, DONG-DEUK;LEE, KOOK-KYUNG;KIM, SOON-AE;HAN, BEOM-SEOK;PARK, YOUNG-IN
Journal of Microbiology and Biotechnology
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v.14
no.6
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pp.1286-1294
/
2004
In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (Hrev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).
Jeong J. Y.;Koo B. C.;Kim N. H.;Kwon M. S.;Park S. H.;Kim T. O.
Reproductive and Developmental Biology
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v.28
no.3
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pp.197-202
/
2004
Human PTH (parathyroid hormone) is known to be efficacious for curing osteoporesis. In this study, we attempted to construct genetically modified porcine cell lines that can ultimately be used for donor cells in nuclear transfer-mediated transgenesis. By using retrovirus vectors carrying tetracycline-regulatory expression system and WPRE (woodchuck hepatitis virus posttranscriptional regulatory element) sequence, we could control PTH expression with tetracycline and boost the promoter activity. Considering that low or constitutive expression of the transgene has been one of major problems that needs to be solved in transgenic animal studies, our results could be helpful in successful production of transgenic pigs as bioreactors.
It is controversial whether low calcium intake, commonly associated with osteoporosis, results in calcium accumulation in soft tissues. This study was conducted to investigate the effects of low calcium (Ca) and oxalate (ox) intake on soft-tissue Ca deposits and bone metabolism in ovariectomized (ovx) rats. Eight week old female Sprague-Dawley rats were ovariectomized and divided into four groups. The rats were fed experimental diets containing low (0.1%, w/w) or normal (0.5%, w/w) Ca with or without sodium oxalate (1%, w/w); Sham/NCa, Ovx/NCa, Ovx/LCa, Ovx/NCa-ox, Ovx/LCa-ox for 6 weeks. All ovx rats showed a remarkable increase in body and tissue weight, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, blood urea nitrogen, alkaline phosphatase, and decreases in weight, ash, and Ca contents, as well as bone breaking force compared to those in sham rats. Serum Ca concentration was not significantly affected by dietary Ca levels or ox intake. Kidney Ca, ox acid content, and microscopic Ca deposition increased remarkably in the Ovx/LCa-ox group compared to those in the other groups. Ca content in the spleen and aorta also increased significantly, but the weight contents, Ca, bone breaking force, and Ca and oxalic acid in feces decreased significantly in the Ovx/LCa-ox group. Serum parathyroid hormone levels were not significantly different among the groups. These results indicate that low Ca intake decreased bone mineral content and increased Ca deposits in soft tissues, which was aggravated by ox intake in ovx rats. Thus, high ox intake may result in a kidney disorder in patients with osteoporosis who eat a low Ca diet.
The purpose of this study was to investigate nutrient intake and bone status in rural postmenopausal women in Korea. Ten postmenopausal women in An-Sung area participated in this study and they were divided into two groups ; women in group I had been postmenopausal for 4 years or less and those in group II had been postmenopausal for 5 years or more before the present study began. Their environmental factors and dietary intakes were surveyed through the personal interviews. Serum levels of calcium, phosphorus, parathyroid hormone(PTH), estradiol and urinary Ca, P, creatinine, hydroxyproline levels were measured from December 4 to December 27 in 1993. The reults of this study are summarized as follows : Average ages of group I and II were 54.8 and 57.2 years. Average menopausal ages of group I and II were 50.8 and 47.3 years. The nutrient intakes of subjects were higher than recommended dietary allowances(RDA) except calorie, protein, calcium, and vitamin A. The nutrient status did not show any significant difference between group I and II. Serum levels of Ca, P, PTH, estradiol and urinary P, creatinine excretion did not show any significant difference between group I and II, and all levels were in normal range. Urinary Ca excretion(p<0.05) and hydroxyproline excretion(p<0.01) were significantly lower in group I than in group II. Urinary Ca/creatinine(Ca/cr) and hydroxyproline/creatinine(Hpr/cr) rations were significantly higher in group II than in group I(p<0.01. And Hpr/cr levels of group I were in normal range, but most of subjects in group II were higher than 0.017 indicating sign of osteoporosis. Correlations between parameters showed that serum PTH adn urinary Ca, Ca/cr levels were positive related (p<0.01), and the years of the after menopausal year and urinary Hpr/cr was also positive related(p<0.05). The present results suggests that it is difficult to protect postmenopausal women's bone destruction having Korean usual diets. Therefore, to prevent osteoporosis with aging, minimizing the hormonal changes in postmenopausal women is needed as well as Ca supplementation and proper exercise before menopause begins.
To investigate the effects of dietary patterns on bone mineral density and its biochemical markers among Korean healthy college women for 2 years, 34 female college students were recruited through convenience sampling. Bone mineral density was measured using Dual Energy X-ray Absorptiometry (DEXA) twice at baseline and two years later. Osteocalcin and parathyroid hormone were measured in fasting serum and N-teleopeptides of type collagen (NTx) in urine. Dietary intake was assessed by 24-hour recall method 8 times with average 4-month interval. Dietary patterns with percent energy of each food group using cluster analysis were classified into two groups. The first cluster (n = 16) was characterized with high consumption of bread, snack, fast foods, beverage and considerable of rice so it was determined as 'Modified dietary pattern group'. The second cluster was characterized with high consumption of rice and kimchi so determined as 'Traditional dietary pattern group'. There were no significant difference of age, menarcheal age, body mass index but percent of body fat by pattern groups. The traditional group showed higher value of bone mineral density among lumber spine and all femur sites at baseline and 2 years later but it was not significant after adjusted for percent of body fat. Serum osteocalcin and urine NTx was higher among the traditional group at baseline than the modified group. There were similar proportions of carbohydrate:fat:protein between groups but significantly higher intake of protein, iron, vitamin A among the traditional group. In conclusion, there were two distinctive dietary patterns among Korean college women. There was difference of bone mineral density and its biochemical markers between two patterns. Further research would be necessary to explore the relationship between dietary patterns and health risks for larger-sized and various populations.
The effects of dietary calcium levels on the blood pressure and calcium metabolism were investigated. Nine normotensive female college students having hypertention family history were participated in 4-week dietary expeiments. They were provided with either high Ca diet (HCa, average 797mg/day) or low Ca diet(LCa, average 225mg/day) during two weeks, each, consecutively. Sodium amounts of the body diets were 3566~4022mg/day, which were ordinary sodium intake levels in Korea. After the HCa, systolic blood pressures(SBR) in both seated and isogrip-seated postitions were decreased by about 2.5mgHg, comparing with those after the LCa(p<.05). Diastoilc blood pressures(DBP) were not changed by dietary calcium levels. Serum total Ca, ionized Ca, Mg and P levels and Ca/Mg ratio were not different between the HCa and the LCa. Serum parathyroid hormone(PTH) levels were similar between two diets, but individually in seven of nine subjects, the slightly lower values of PTH were observed after the HCa than after the LCa. Urinary excretion of Ca(p<.01), Mg(p<.05) and P(p<.1) were increased after the HCa comparing with the LCa, but Ca/Mg ratio were not different between the two diets. SBP was in positive correlations with boty urinary excretion of Ca(supine, r=.7356, p<.05) and urinary Ca/Mg ratio(isogrip-seated, r=.7483, p<.05). SBP was also negatively correlated with serum P level(supine, r=-.6930, p<.05) and DBP was in negative correlation with urinary P excretion(seated, r=-.8586, p<.01). Serum total and ionized Ca, Mg, Ca/Mg ratio were not significantly correlated with blood pressures.
Kim, Mi-Ri;Yang, Won-Kyung;Grzesik, Wojciech;Ko, Hyun-Jung
International Journal of Oral Biology
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v.33
no.3
/
pp.113-116
/
2008
Cementum is the mineralized tissue of the tooth. It is similar to bone in several aspects but it differs from bone. Human bone marrow stromal cells (BMSC) and human cementum derived cells (HCDC) (10,000 $cells/cm^2$) were plated in 6 well plates as feeder cells. The next day, mouse bone marrow cells (1.5 million $cells/cm^2$) were added. One group of these plates were incubated in serum-free conditioned medium (SFCM) generated from BMSC or HCDC supplemented with 2% FBS, parathyroid hormone (PTH), 1, 25 dihydroxyvitamin $D_3$ (Vit. $D_3$) and dexamethasone, or plain medium with the same supplements. Another group of plates were cocultured with BMSC or HCDC in plain medium supplemented with 2% FBS, PTH, Vit. $D_3$ and dexamethasone. Plates grown without SFCM or coculture were used as controls. After 10 days, the cells were stained for tartrate-resistant acid phosphatase (TRAP). BMSC were found to support osteoclast formation under normal conditions. This was inhibited however by both SFCM generated from HCDC and also by coculture with HCDC. In addition, HCDC themselves did not support osteoclast formation under any conditions. Our results thus indicate that HCDC do not support osteoclast formation in vitro and that soluble factor (s) from HCDC may inhibit this process. In addition, we show that this inhibition also involves an active mechanism that is independent of osteoprotegerin, a feature that may distinguish cementoblasts from other cells present in periodontium.
Rickets is a nutritional disorder which is caused either by deficiency of vitamin D or by a defective activation of vitamin D. In these days, even though the incidence of rickets has decreased through adequate nutritional support, we sometimes experience rickets in babies receiving a prolonged special diet as therapy for chronic diarrhea, or those subject to a in receiving the prolonged elimination of milk because of allergy. But there are no reports about rickets caused by absolute elimination of milk because of allergies in Korea. We report here a case of rickets developed after feeding on Sunsik( a mixture of several grain and fruits powder) during a seven months period in an 8-month-old male patient. This male infant manifested vomiting, poor feeding, decreased serum calcium and 25-hydroxycholecalciferol levels, and markedly increased serum alkaline phosphatase and parathyroid hormone levels. Skeletal X-rays showed cupping and fraying in distal metaphyses of radius and ulna, and generalized osteopenia. The patient improved with vitamin D and calcium therapy.
Background: Sevelamer is associated with reduced complications of chronic kidney disease-mineral bone disorder (CKD-MBD) resulted from hyperphosphatemia, which may contribute mortality, in CKD patients with dialysis. So far clinical outcomes of sevelamer on mortality and risk of cardiovascular mortality related to CKD-MBD are debating. Purpose of this study was to evaluate the effectiveness of sevelamer HCl on mortality of secondary hyperparathyroidism (SHPT), risk of cardiovascular mortality and, frequency of osteopathy in end stage renal disease (ESRD) patients with dialysis. Methods: We retrospectively reviewed the electronic medical records of 536 patients with ESRD, who were admitted for moderate to severe SHPT, for 36 months. 75 patients who met inclusion criteria were evaluated for the efficacy of sevelamer (mean serum iPTH = 487.5 pg/mL). Results: Sevelamer intervention was not associated with increased three-year survival time compared with non-sevelamers group [average survival month: 30.4 months in sevelamer group, 26.8 months in non-sevelamer group, p = 0.463]. Sevelamer intervention was not associated with significant mortality benefit and cardiovascular mortality benefit as compared to non-sevelamer group [sevelamer group: non-sevelamer group, all-cause mortality (iPTH > 600 pg/mL): 14.3% (1/34): 20% (1/41) p = 0.962, OR = 0.935, 95% CI, 0.058-14.98, heart disease mortality: 6.67% (2/30): 0% (0/32) p = 0.138]. Sevelamer was not associated with significantly lower cumulative incidence of osteopathy compared to non-sevelamer group (sevelamer group: non-sevelamer group, 5.9% (2/34):9.8% (4/41); p = 0.538; OR = 0.578; 95% CI, 0.099-3.367). Conclusion: Sevelamer was not associated with decreased all-cause mortality and risk of cardiovascular mortality compared to non-sevelamer group in ESRD patients with SHPT.
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