• Clinical and Experimental Pediatrics
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• v.48 no.3
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• pp.306-309
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• 2005

Purpose : The aim of study is to investigate the clinical manifestations and the etiology of markedly-elevated serum alkaline phosphatase(ALP) levels in children without accompanying liver or bone disease. Methods : The serum ALP and other biochemical laboratory data of 4,989 patients attending the pediatric department of Ewha Womans University Mokdong Hospital between January 2002 to December 2002 were studied. The subjects' ages ranged from 4 months to 14 years. Among them, serum ALP levels were markedly elevated over 1,000 IU/L in 114 children. Among those 114 children, 97 children without liver or bone disease were reviewed retrospectively. Results : Of the 114 children with serum ALP activity of over 1,000 IU/L, 97(85.8 percent) children had neither liver or bone disease. The average ALP activity level was $1,539{\pm}948IU/L$. The male : female ratio was 1 : 0.7. Forty-four children(45.3 percent) were between 4 months to 1-year-old, 19 children(19.3 percent) were between 1- to 2-year-old. We observed a seasonal clustering of cases in during October with 10 cases(10.2 percent) and in during December with 11 cases(11.3 percent). The most common clinical presentation was respiratory tract infection in 25 cases(26.9 percent), and acute gastroenteritis in 17 cases(17.5 percent). Forty-four cases had follow-up ALP activity level, 1 month later and the activity decreased under 1,000 IU/L in 37 cases(84 percent). Conclusion : Hyperphosphatasemia is a benign and transient phenomenon. If there are no clinical and laboratory abnormalities of liver and bone, we suggest monitoring monitor the high serum ALP level 1 month later. If decreased, it seems that it is not necessary for specific examinations to exclude other diseases of malignant condition.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.4
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• pp.18-44
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• 2017

Purpose: The object of this study was to observe the anti-climacterium activity of Gagamguibiondam-tang (GGOT) on ovariectomized (OVX) rats, a well-documented rodent models resembles with women postmenopausal climacterium symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis, organ steatosis and mental disorders. Methods: In this study, anti-climacteric effects were evaluated separated into three categories; 1) anti-obese, 2) anti-uterine atrophy and 3) anti-osteoporotic effects. Five groups were used (8 rats in each group); sham control, OVX control, GGOT 500, 250 and 125 mg/kg administered groups. Twenty-eight days after bilateral OVX surgery, GGOT were orally administered, once a day for 84 days, and then the changes on the body weight and gain during experimental periods, serum estradiol levels, abdominal fat pad and uterus weights with histopathology of abdominal fat pads (total thickness and mean adipocyte diameters) and uterus (total, epithelial and mucosal thickness, percentages of uterine gland regions) for anti-obese and estrogenic effects. In addition, femur, tibia and fourth or fifth lumbar vertebrae (L4 or L5) wet, dry and ash weights, mineral density (BMD), bone strength (failure load), serum osteocalcin and bone specific alkaline phosphatase (bALP) contents, histological and histomorphometrical analyses - bone mass and structure with bone resorption, were monitored for anti-osteoporosis activity. Results: As a result of OVX, noticeable increases of body weight and gains, food and water consumption, weights of abdominal fat pad deposited in dorsal abdominal cavity, serum osteocalcin levels were demonstrated in this experiment with decrease of uterus, femur, tibia and L5 weights, serum bALP and estradiol levels. In addition, marked hypertrophic changes of adipocytes located in deposited abdominal fat pads, uterine disused atrophic changes, decreases of bone mass and structures of femur, tibia and L4 were also observed in OVX control rats with dramatic increases of bone resorption markers, the Ocn and OS/BS at histopathological and histomorphometrical analysis in this study as compared with sham-operated control rats, suggesting the estrogen-deficient climacterium symptoms - obese and osteoporosis were induced by OVX, respectively. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by 84 days of continuous oral treatment of GGOT 500, 250 and 125 mg/kg, respectively. Especially, GGOT 500, 250 and 125 mg/kg showed clear dose-dependent inhibitory activities on the OVX-induced climacterium signs. Conclusion: The results suggest that oral administration of GGOT 500, 250 and 125 mg/kg has clear dose-dependent favorable anti-climacterium effects - estrogenic, anti-obese and anti-osteoporotic activities in OVX rats in this experiment.

• Korean Journal of Clinical Pharmacy
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• v.18 no.2
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• pp.114-119
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• 2008

Alendronate is a bisphosphonate that selectively inhibits osteoclast-mediated bone resorption. Dosing convenience is an important element for the enhancement of patient compliance and the effective management of osteoporosis. The purpose of this study was to compare the effectiveness and compliance among alendronate pharmaceutical products (oral once-weekly alendronate 70 mg, daily alendronate 10 mg, and once-weekly alendronate 70 mg with Vitamin $D_3$ 2800 IU) in terms of the change in bone mineral density (BMD), biochemical markers, and compliance estimates. A retrospective chart review was conducted in patients with osteoporosis who received alendronate 70 mg (Group 1), alendronate 10 mg (Group 2), or alendronate 70 mg with Vitamin D3 2800 IU (Group 3) at the endocrinology department of a hospital in Korea from Jan. 1, 1998 to Mar. 31, 2008. The primary endpoints were the increases in spine antero-posterior BMD T-score and femur trochanter BMD T-score, and the compliance of alendronate products. Secondary endpoints included changes in bone turnover-related biochemical markers including bone-specific alkaline phosphatase, urinary N-terminal telopeptides (NTX) and osteocalcin, and in serum vitamin $D_3$ concentration. There was no statistical difference in the BMD increase among the three alendronate products; spine BMD T-score increased by $0.49{\pm}0.52$, $0.39{\pm}0.48$ and $0.50{\pm}0.41$, and femur trochanter BMD T-score by $0.29{\pm}0.42$, $0.21{\pm}0.53$ and $0.24{\pm}0.22$ in Group 1, 2 and 3, respectively. With respect to the increases in femur trochanter BMD T-score and the decreases in NTX and osteocalcin, 70 mg once-weekly group was remarkably superior to 10 mg daily group (p < 0.05) The compliance of 70 mg once-weekly group was significantly higher than that of 10 mg daily treatment group (p < 0.001). In conclusion, all three alendronate treatment groups were equivalent in effectiveness, and the compliance of 70 mg once-weekly group was better than that of 10 mg daily treatment group.

• Journal of Periodontal and Implant Science
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• v.42 no.3
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• pp.73-80
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• 2012

Purpose: The purpose of this study was to investigate the effects of the immunosuppressants FK506 and cyclosporin A (CsA) on the osteogenic differentiation of rat mesenchymal stem cells (MSCs). Methods: The effect of FK506 and CsA on rat MSCs was assessed in vitro. The MTT assay was used to determine the deleterious effect of immunosuppressants on stem cell proliferation at 1, 3, and 7 days. Alkaline phosphatase (ALP) activity was analyzed on days 3, 7, and 14. Alizarin red S staining was done on day 21 to check mineralization nodule formation. Real-time polymerase chain reaction (RT-PCR) was also performed to detect the expressions of bone tissue-specific genes on days 1 and 7. Results: Cell proliferation was promoted more in the FK506 groups than the control or CsA groups on days 3 and 7. The FK506 groups showed increased ALP activity compared to the other groups during the experimental period. The ALP activity of the CsA groups did not differ from the control group in any of the assessments. Mineralization nodule formation was most prominent in the FK506 groups at 21 days. RT-PCR results of the FK506 groups showed that several bone-related genes-osteopontin, osteonectin, and type I collagen (Col-I)-were expressed more than the control in the beginning, but the intensity of expression decreased over time. Runx2 and Dlx5 gene expression were up-regulated on day 7. The effects of 50 nM CsA on osteonectin and Col-I were similar to those of the FK506 groups, but in the 500 nM CsA group, most of the genes were less expressed compared to the control. Conclusions: These results suggest that FK506 enhances the osteoblastic differentiation of rat MSCs. Therefore, FK506 might have a beneficial effect on bone regeneration when immunosuppressants are needed in xenogenic or allogenic stem cell transplantation to treat bone defects.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.8
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• pp.1171-1175
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• 2005

An experiment was conducted (28 to 44 weeks) to study the laying performance, shell quality, and nutrient retention of White Leghorn layers fed different levels of non-phytate phosphorus (NPP). Six levels of NPP (0.15, 0.18, 0.21, 0.24, 0.27 and 0.30%) at a constant calcium (Ca) level (3.5%) in maize-soya-deoiled rice bran based diets were formulated, and each experimental diet was offered ad libitum for 16 weeks to five replicates with five birds in each replicate. The body weight of WL layers fed diet containing 0.15% NPP was significantly (p<0.05) lower than those fed diet with 0.30% NPP, at 44 weeks of age. However, the hen day egg production, egg weight, daily feed intake and feed consumed per dozen eggs were not influenced by the variation in the NPP levels in the diet. The bone ash content was significantly (p<0.05) higher in the birds fed 0.30% NPP as compared with those fed diets up to 0.24% NPP. Bone ash content was intermediate in the birds fed diet containing 0.27% NPP. The tibia strength followed the same trend as that of bone ash. Dietary NPP content had no influence on serum Ca and protein concentration and activity of alkaline phosphatase. However, serum inorganic P concentration increased linearly with NPP content in the diet. The concentration of P was significantly (p<0.05) higher in the birds fed 0.27% NPP or higher as compared with those fed 0.15% NPP. Levels of dietary NPP had no influence on egg quality parameters like shell wt, shell thickness, shell strength and specific gravity. The retention of nutrients such as DM, N and Ca were comparable among the WL layers fed different levels of NPP. However, the retention of P decreased linearly with increase in the level of NPP in the diet. The retention of P in the birds fed diets up to 0.24% NPP in the diet was comparable, however further increasing the content of NPP (either 0.27% or 0.30%) reduced the retention of P. Based on the results of the present study, 0.15% NPP (180 mg/b/d) in the diets of WL layers is adequate for optimum production performance during 28 to 44 weeks of age, however, WL layers require 0.27% NPP (324 mg /b/d) in the diet for optimum production with better bone mineralization.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.55-62
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• 2005

Very little research has been carried out on safflower seed for the prevention and treatment of the bone deficiency diseases, including osteoporosis, which are supported by scientific evidences. In the present study, $3{\mu}l$ of 0.1% dried crude extract or $2{\mu}l$ of 0.1% dried aqueous fraction were shown to significantly accelerate the rate of differentiation of osteoblast. Also, the crude extract and aqueous fraction increased the $[Ca^{2+}]_i$ of the cultured osteoblast cells: $3{\mu}l$ of 0.1% dried crude extract and $2{\mu}l$ of 0.1% dried aqueous fraction significantly increased the $[Ca^{2+}]_i$ of the cultured osteoblast cells ($8{\times}10^{-4}$) to the extent that it deserves a considerable attention. Furthermore, the crude extract and aqueous fraction increased the $[Ca^{2+}]_i$ of the cultured osteoblast cells, and $300{\mu}M$ $Cd^{2+}$, specific calcium channel blocker, completely blocked the increase. Therefore, the increased $[Ca^{2+}]_i$ of the cultured osteoblast cells by safflower seed component continued to activate calcium channel.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.123-131
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• 2016

Osteoporosis is a bone pathology leading to increased fracture risk and challenging the quality of life. The aim of this study was to evaluate the effect of an anthraquinone glycoside, aloin, on osteogenic induction of MC3T3-E1 cells. Aloin increased alkaline phosphatase (ALP) activity, an early differentiation marker of osteoblasts. Aloin also increased the ALP activity in adult human adipose-derived stem cells (hADSC), indicating that the action of aloin was not cell-type specific. Alizarin red S staining revealed a significant amount of calcium deposition in cells treated with aloin. Aloin enhanced the expression of osteoblast differentiation genes, Bmp-2, Runx2 and collagen 1a, in a dose-dependent manner. Western blot analysis revealed that noggin and inhibitors of p38 MAPK and SAPK/JNK signals attenuated aloin-promoted expressions of Bmp-2 and Runx2 proteins. siRNA mediated blocking of Wnt-5a signaling pathway also annulled the influence of aloin, indicating Wnt-5a dependent activity. Inhibition of the different signal pathways abrogated the influence of aloin on ALP activity, confirming that aloin induced MC3T3-E1 cells into osteoblasts through MAPK mediated Wnt and Bmp signaling pathway.

• Development and Reproduction
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• v.15 no.4
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• pp.281-289
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• 2011

The objective of this study was to investigate the effective cryoprotectants for the cryopreservation of porcine mesenechymal stem cells (pMSCs). In order to understand the effectiveness of various cryoprotectants on pMSCs, we studied the most commonly used cryoprotectants; dimethyl sulfoxide (DMSO), ethylene glycol (EG), DMSO and EG. pMSCs were isolated from bone marrow matrix of piglet (2 month) and characterized by alkaline phopshatase (AP) activity, colony forming, and differentiation to adipocyte. In slow cooling cryopreservation, the pMSCs were exposed to cell medium containing Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% DMSO, 1.5M EG and 5% DMSO/0.75M EG, respectively, and freezed to $-1^{\circ}C$/min from $25^{\circ}C$ up to $-80^{\circ}C$ in a cryo-container. The proportion of viable cells and the growing rates in fresh pMSCs were significantly (P<0.05) higher than those of other groups, but did not differ between the cryopreserved groups. The expression of Sox-2 and Nanog gene was increased by extending culture time in cryopreserved groups. The expression of Bax gene in cryopreserved groups was similar with fresh pMSCs. Moreover, the gene expression of adipocyte-specific marker as well as chondrogenic/osteogenic factors in cryopreserved groups was similarly to fresh pMSCs. Taken together, our results suggested that all these cryoprotectants of 10% DMSO, 1.5M EG and 5% DMSO/0.75M EG could be used for cryopreservation of the pMSCs.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.811-817
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• 2009

Purpose : Inhaled corticosteroids (ICS) are used as first-line agents for the treatment of persistent asthma; however, their use is accompanied by apprehension of potential systemic adverse effects. This study aimed to assess the effects of ICS on bone mineral density (BMD) and bone metabolism in children with asthma. Methods : From February 2008 to September 2008, 26 asthmatic children treated with ICS (ICS group), 15 asthmatic children treated with leukotriene receptor antagonist (LTRA) (LTRA group), and 30 healthy children (Control group) were selected from the Korea University Anam Hospital. BMD and serum bone-specific alkaline phosphatase (BALP) levels were measured. The asthmatic children underwent spirometry and methacholine bronchial challenge test. Results : There were no significant differences in BMD in the lumbar spine (P=0.254) and proximal femur (P=0.297) among the 3 groups. The serum BALP levels were significantly higher in both the ICS (P=0.017) and LTRA (P=0.025) groups than in the Control group. None of the parameters pertaining to ICS use, such as the mean daily dose during the last 6 months, the total cumulative dose, duration of use, and age of commencement of use, showed significant correlations with BMD (P>0.05 for all parameters). Conclusions : We demonstrated that a low dose of ICS does not exert any significant adverse effect on bone metabolism in asthmatic children. These findings support the current recommendations with regard to the use of ICS for asthmatic children.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.3
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• pp.197-205
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• 2007

Angiogenesis is a essential part for bone formation and bone fracture healing. Vascular endothelial growth factor (VEGF), one of the most important molecules among many angiogenic factors, is a specific mitogen for vascular endothelial cells. VEGF-mediated angiogenesis is required for bone formation and repair. However, the effect of VEGF on osteoblastic cells during osteogenesis is still controversial. In recent days, substantial progress have been made toward developing tissue-engineered alternatives to autologous bone grafting for maxillofacial bony defects. Periosteum has received considerable interest as a better source of adult stem cells. Periosteum has the advantage of easy harvest and contains various cell types and progenitor cells that are able to differentiate into a several mesenchymal lineages, including bone. Several studies have reported the bone formation potential of periosteal cells, however, the correlation between VEGF signaling and cultured human periosteal cell-derived osteogenesis has not been fully investigated yet. The purpose of this study was to examine the correlation between VEGF signaling and cultured human periosteal-derived cells osteogenesis. Periosteal tissues of $5\;{\times}\;20\;mm$ were obtained from mandible during surgical extraction of lower impacted third molar from 3 patients. Periosteal-derived cells were introduced into the cell culture and were subcultured once they reached confluence. After passage 3, the periosteal-derived cells were further cultured for 42 days in an osteogenic inductive culture medium containing dexamethasone, ascorbic acid, and ${\beta}-glycerophosphate$. We evaluated the alkaline phosphatase (ALP) activity, the expression of Runx2 and VEGF, alizarin red S staining, and the quantification of osteocalcin and VEGF secretion in the periosteal-derived cells. The ALP activity increased rapidly up to day 14, followed by decrease in activity to day 35. Runx2 was expressed strongly at day 7, followed by decreased expression at day 14, and its expression was not observed thereafter. Both VEGF 165 and VEGF 121 were expressed strongly at day 35 and 42 of culture, particularly during the later stages of differentiation. Alizarin red S-positive nodules were first observed on day 14 and then increased in number during the entire culture period. Osteocalcin and VEGF were first detected in the culture medium on day 14, and their levels increased thereafter in a time-dependent manner. These results suggest that VEGF secretion from cultured human periosteal-derived cells increases along with mineralization process of the extracellular matrix. The level of VEGF secretion from periosteal-derived cells might depend on the extent of osteoblastic differentiation.