• BMB Reports
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• v.55 no.12
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• pp.627-632
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• 2022

Dickkopf-1 (DKK1) is a secreted protein that acts as an antagonist of the canonical WNT/β-catenin pathway, which regulates osteoblast differentiation. However, the role of DKK1 on osteoblast differentiation has not yet been fully clarified. Here, we investigate the functional role of DKK1 on osteoblast differentiation. Primary osteoprogenitor cells were isolated from human spinal bone tissues. To examine the role of DKK1 in osteoblast differentiation, we manipulated the expression of DKK1, and the cells were differentiated into mature osteoblasts. DKK1 overexpression in osteoprogenitor cells promoted matrix mineralization of osteoblast differentiation but did not promote matrix maturation. DKK1 increased Ca⁺ influx and activation of the Ca⁺/calmodulin-dependent protein kinase II Alpha (CAMK2A)-cAMP response element-binding protein 1 (CREB1) and increased translocation of p-CREB1 into the nucleus. In contrast, stable DKK1 knockdown in human osteosarcoma cell line SaOS2 exhibited reduced nuclear translocation of p-CREB1 and matrix mineralization. Overall, we suggest that manipulating DKK1 regulates the matrix mineralization of osteoblasts by Ca⁺-CAMK2A-CREB1, and DKK1 is a crucial gene for bone mineralization of osteoblasts.

• Preventive Nutrition and Food Science
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• v.9 no.1
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• pp.45-52
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• 2004

Effects of dietary calcium lactate (CaL-A) and Chungkukjang (Korean native fermented soybean) on bone mass, calcium status, body weight, serum glucose and cholesterol levels in young male rats were investigated. Chungkukjang was fermented by mixing 4 types of Bacillus sp., and then dried at 45$^{\circ}C$. Calcium lactate was prepared from the ash of black snail. The rats were fed a commercial rat diet for 1 week and then the experimental diets for 4 weeks. Animals were divided into four dietary groups: one calcium-deficient diet (Ca-De) and one of three with calcium supplemented diets (5 g calcium/kg diet) with either calcium phosphate (Ca-P), CaL-A, or CaL-A + Chuntkukjang (CaL-AC). Calcium supplemented diets contained 39 g Ca-P/kg diet and 28 g/kg of calcium lactate in the CaL-A and CaL-AC diets. Body weight gains during the 4 weeks in the Ca-P, CaL-A, CaL-AC and Ca-De groups were 130.45 g,112.50 g, 143.40 g and 10.20 g, respectively. Feed consumption of the groups from high to low was CaL-AC > Ca-P > CaL-A > Ca-De. The Ca-De group had low femur weights and low serum calcium concentrations, while they were comparatively high in CaL-AC, Ca-P and CaL-A groups. The Ca-De groups excreted less calcium in urine than did the other rats, probably due to increased absorption of the mineral in Ca-P, CaL-A and CaL-AC groups. Microscopic observations revealed that there were many regularly spaced holes in the femur of Ca-De group, while there were much smaller regularly spaced holes in Ca-P group. However, no holes in femur were observed in the CaL-A and CaL-AC groups. Bone surfaces were especially smooth and clean in the CaL-AC group. Serum concentrations of glucose and total cholesterol were remarkably lower in the CaL-AC group than in the other supplemented groups. These results suggest that calcium from CaL-A has higher bioavailability than from Ca-P, and dietary Chungkukjang may have a beneficial effect on calcium metabolism.

• Nutrition Research and Practice
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• v.7 no.5
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• pp.409-417
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• 2013

This study was performed to determine the effects of dietary calcium (Ca) intake, milk and dairy product intake, and serum vitamin D level on bone mineral density. The survey data from the 2008-2009 Korea National Health and Nutrition Examination Survey (KNHANES) for adults (3,819 males, 5,625 females) aged > 20 years were examined; osteoporosis was defined according to the standards for Asian populations (T-score < -2.5). The risk for osteoporosis significantly decreased as Ca intake increased; this effect persisted (quartile 4 vs. quartile 1 of Ca intake: odds ratio [OR] 0.66; 95% confidence interval [CI]: 0.50-0.87) even after adjustment for gender, age, and other factors (body mass index, serum vitamin D, menstruation, female hormone intake, menopausal status, and the number of days per week of muscular strength exercise). Additionally, the risk for osteoporosis significantly decreased as the Ca/P ratio increased (quartile 4 vs. quartile 1: OR 0.76; 95% CI: 0.58-0.98). The degree of risk was 0.96 (0.66-1.38) in those who consumed < 1 portion of milk or dairy products daily, and 0.71 (0.53-0.96) in those who consumed > 1 portion per day, compared with those who had zero intake. The risk for osteoporosis significantly decreased as the serum 25(OH) vitamin D level increased. From these results, we advocate an increase in Ca, milk, and dairy product intake, and that serum 25(OH) vitamin D levels be maintained within the normal range, for the maintenance of bone health and the prevention of osteoporosis in adults.

• Korean Journal of Community Nutrition
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• v.10 no.4
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• pp.536-545
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• 2005

This study was conducted to investigate osteopenia and osteoporosis prevalence of radius and tibia using Quantitative Ultrasound (QUS) and to identify affecting factors of osteoporosis. A total of 4,340 women aged 40 - 69 years, living in Ansung (rural) and Ansan (mid-sized) area, and free of illnesses affecting bone metabolism participated in the community-based cohort study. Among them 4,059 subjects measured radius bone density and 4,089 measured tibia. The T-score threshold, defined as < -1.0 and $\le$-2.5, was used to identify subjects with osteopenia and osteoporosis by WHO criteria. The crude prevalence of osteoporosis in radius and tibia was $8.4\%$ and $23.3\%$ respectively; after adjustment for age, it changed $6.3\%$ and $18.8\%$. In simple logistic regression analysis, the prevalence of osteoporosis increased by aging, non-marital status, low education, low income. Otherwise, high intakes of Ca/P, thiamin, riboflavin, vitamin B6, and vitamin E were decreased osteoporosis prevalence. Compared to the normal BMI (body mass index) group 08.5 $\le$ BMI < 23), the odds ratio (ORs) of the low BMI group (BMI < 18.5), and high BMI groups (BMl25-30, BMI $\ge$ 30) were significantly increased. The OR of osteoporosis decreased across increasing quartiles of intakes of Ca, P and Ca/P. Therefore, maintaining normal BMI and increasing Ca intake and Ca/P ratio may have a beneficial effect on bone health of Korean women.

• Nutritional Sciences
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• v.5 no.3
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• pp.155-160
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• 2002

The purpose of this study was to investigate the effects of micronutrient supplementation on the growth of preschool children in China. A double-blind, placebo-controlled trial was conducted on 156 growth retarded preschool children who were randomly assigned to the following five groups : supplemental control (S-control; n=28); zinc supplementation (＋Zn; 3.5mg Zn/day, n=34); zinc and calcium supplementation (＋ZnCa; 3.5mg Zn ＋ 250mg Ca/day, n=37); zinc, calcium and vitamin A supplementation (＋ZnCaVA; 3.5mgZn ＋ 250mgCa ＋ 200gVA/day, n=28); and calcium and vitamin A supplementation (＋CaVA; 250mgCa ＋ 200gVA/day, n=29). Another 34 children of normal height were selected as a normal control (N-control). Supplementation continued for twelve months. After supplementation, the height gains in the ＋Zn group (7.84cm per year) and the ＋ZnCa group (7.70 cm per year) were significantly higher than that in the S-control group (6.74 cm per year, P＜0.05). The weight gain in the ＋ZnCaVA group (2.55kg per year) and the ＋CaVA group (2.57 kg per year) was also significantly higher than that in the S-control group (2.19 kg per year, P＜0.05). The average number of days of illness in each group taking supplements was lower than that in the S-control group (13 days per year compared with 23 days per year). No significant differences in bone maturity were observed between the groups. In conclusion, in this study Zinc and Zinc ＋ Calcium supplementation improved the height gain, and vitamin A improved the weight gain, in growth retarded preschool children, but these supplements did not affect the maturity of bone. Micronutrient supplementation also lowered the morbidity of these children.

• Journal of Nutrition and Health
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• v.29 no.9
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• pp.950-957
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• 1996

This study was designed to investigate the effects of caffeine intake on Ca and P metabolism in ovariectomized rats. For this purpose, the ovariectomized female rats weighing 230.8$\pm$3.5g were divided into four groups, eight rats each ; control, low caffeine(LC), medium caffeine(MC)and high caffeine(HC) groups. They were supplied for six weeks with the caffeine of 0mg, 66.8mg, 167mg and 334mg per kilogram of diet, respectively, and the results are summarized as follows. 1) There were no significant differences in feed intake, feed efficiency ratio and body weight change among all of experimental groups. But liver weight(both total weight and weight/body weight) was significantly decreased by caffeine in MC group. 2) The weight of tibia was decreased by caffeine intake in MC and HC groups. But the length, Ca and P content of tibia and femur was not changed in all of caffeine groups. 3) Ca, PTH and calcitonin levels in serum were not affected by caffeine. While, serum P level in HC group was significantly increased as compared with the control. 4) The fecal excretion of Ca and P tended to be higher in the caffeine groups, and as the result, the absorption rate, retention and retention rate of Ca and P tended to be decreased. It was noteworthy that P retention was significantly lowered in HC group as compared with LC group. The results showed that, when caffeine was taken by ovarietomized rats, the weight of tibia was decreased and the retention rate of Ca and P tended to be lowered. Therefore, too much intake of caffeine for women whose bone mineral density of tibia is decreased after postmenopause seems to accelerate the decrease of bone mineral density due to the negative effect on metabolism of Ca and P.

• Journal of Nutrition and Health
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• v.28 no.4
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• pp.298-308
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• 1995

To investigate the effect of estrogen and dietary protein level on Ca metabolism, female rats were undergone ovariectomy or sham-operation. Ovariectomized rate were divided into either estrogen-or vehicle-treated groups. Each treatment group was again divided into 40%-casein(H) or 10%-casein(L) diet groups. All experimental diets contained 0.2% Ca, 0.4% P and fed to rats for 8 weeks. Apparant Ca absorption and Ca balance were not affected by dietary protein level and ovariectomy, however they were increased by estrogen injection and this effect was even higher in low protein groups. Urinary Ca excretion were higher in high protein groups. GFR was not affected by dietary protein level, ovariectomy, or by estrogen injection. Urinary protein excretion was higher in high protein groups, which implies that the kidney funtion was deteriorated by high protein diet, and this may account partly for the higher urinary Ca in high protein groups. Ovariectomy or estrogen treatment had no effect on urinary protein excretion. Urinary hydroxyproline was higher in ovariectomized rats and increased in high protein grous. Elevated value of ovarictomized rats was lowered by estrogen injection, especially in low protein group. Alkaline phosphatase tended to increase in ovariectomized groups and lowered with estrogen treatment, but this difference was not statistically significant. Serum PTH was not affected by ovariectomy and dietary protein level. Therefore the increased hydroxproline excretion does not seem to be attributed to PTH. Dietary protein level, ovariectomy and estrogen treatment did not affect the weights and components of femur, scapular, and 4th vertebra. Ash/wt ratio of femur was, however, lower in ovariectomized rats and increased with estrogen treatment. Therefore, among the bones studied, femur seemed to be the most vulnerable. The results of this study shows that estrogen treatment may alleviate or reduce bone loss in postmenopausal women somewhat, especially for those people with low protein diet.

• Journal of Periodontal and Implant Science
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• v.47 no.4
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• pp.194-210
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• 2017

Purpose: The aim of the present study was to evaluate the healing of post-extraction sockets following alveolar ridge preservation clinically, radiologically, and histologically. Methods: Overall, 7 extraction sockets in 7 patients were grafted with demineralised bovine bone mineral and covered with a porcine-derived non-crosslinked collagen matrix (CM). Soft tissue healing was clinically evaluated on the basis of a specific healing index. Horizontal and vertical ridge dimensional changes were assessed clinically and radiographically at baseline and 6 months after implant placement. For histological and histomorphometric analysis, bone biopsies were harvested from the augmented sites during implant surgery 6 months after the socket preservation procedure. Results: Clinically, healing proceeded uneventfully in all the sockets. A trend towards reduced horizontal and vertical socket dimensions was observed from baseline to the final examination. The mean width and height of resorption were 1.21 mm (P=0.005) and 0.46 mm (P=0.004), respectively. Histologically, residual xenograft particles ($31.97%{\pm}3.52%$) were surrounded by either newly formed bone ($16.02%{\pm}7.06%$) or connective tissue ($50.67%{\pm}8.42%$) without fibrous encapsulation. The CM underwent a physiological substitution process in favour of well-vascularised collagen-rich connective tissue. Conclusions: Socket preservation using demineralised bovine bone mineral in combination with CM provided stable dimensional changes of the alveolar ridge associated with good reepithelialisation of the soft tissues during a 6-month healing period.

• Journal of the Korean Society of Food Culture
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• v.23 no.6
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• pp.801-811
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• 2008

The principal objective of this study was to assess the effects of soy isoflavone supplementation on bone mineral density in 36 female college students with osteopenia for 12 weeks. The subjects were divided into three groups on the basis of bone mineral density. The experimental groups were provided supplements of either 80 mg of isoflavone (Iso-80) or 40 mg of isoflavone (Iso-40). To the placebo group, 40 mg of powdered glutinous rice was administered. It was determined that many subjects with osteopenia evidenced lower levels of activity as compared to the control group. Isoflavone supplementation was more effective in controlling total cholesterol and LDL-cholesterol than was observed in the placebo group. We noted no significant differences in serum osteocalcin concentration between Iso-40 and the placebo group, but significant differences in osteocalcin concentration were detected between Iso-80 and the placebo group. Bone quality indices (BQI) were correlated positively with mineral content, lean body mass, muscular mass, and blood components including albumin, Ca, Mg, ALPase, and osteocalcin. Both Iso-40 and Iso-80 supplementation for 12 weeks significantly increased protein and mineral content in the body. As lower intakes of Ca and folate were noted in the subjects, emphasis should be given to adequate intakes of these nutrients in the subjects. In conclusion, 12 week isoflavone supplementation in young females with osteopenia exerted positive effects on bone mineral density and bone turnover markers.

• Journal of Nutrition and Health
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• v.36 no.5
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• pp.459-469
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• 2003

We examined the effects of calcium intake levels on mineral metabolism during pregnancy using calcium-deficient young adult rats. Five week-old female Sprague-Dawley rats were fed normal Ca (NCa, 0.5%) and low Ca (LCa, 0.15%) diets for five weeks (pre-pregnancy). The low Ca intake group was then divided into three groups and fed low Ca (0.15%), normal Ca (0.5%) and high Ca (1.5%) diets for 3 weeks (pregnancy). All of the rats were mated with normal male rats. The control group was fed a consistently normal Ca (0.5%) diet during pre-pregnancy and pregnancy. On the day after delivery, dams and their pups were sacrificed. We measured total protein, albumin, alkaline phosphatase and mineral content in serum and weight, length, breaking force, ash and mineral content in the femur and lumbar (L2-L4) of the dams. Whole body mineral content was measured in the pups. There was no difference in weight gain and food intake among the groups. Serum total protein and albumin were in the normal range but a little lower during pregnancy. High Ca supplementation decreased serum Mg and Fe during pregnancy. Weight, ash and Ca of the femur and lumbar significantly decreased in rats fed a chronically low Ca diet during pre-pregnancy and pregnancy. Calcium supplementation levels were above normal during pregnancy and increased the bone weight and breaking force of rats fed the low Ca diet during pre-pregnancy. However, Ca supplementation did not increase the ash and Ca contents in the bones. High Ca supplementation during pregnancy significantly decreased Mg in the bones and increased Ca and P in the kidneys. Ash content of pups from dams fed the chronically low Ca diet decreased but there was no difference in whole body Ca among the groups. Mg and Fe in the whole body decreased in pups from dams fed the high Ca diet. Pregnancy performance was reduced in dams fed the low Ca diet. These results suggest that above normal Ca supplementation levels during pregnancy restored maternal bone status to some extent in rats fed the chronically low Ca diet. The same could not be said for mineral content. Also, high Ca supplementation during pregnancy may deteriorate mineral composition in bones and other tissues. Therefore, more detailed research is needed to facilitate sound recommendations on appropriate calcium intake during pregnancy. (Korean J Nutrition 36(5): 459∼469, 2003)