• Title/Summary/Keyword: 1,25-dihydroxyvitamin D

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Vitamin D dependent rickets type I

  • Kim, Chan-Jong
    • Clinical and Experimental Pediatrics
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    • v.54 no.2
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    • pp.51-54
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    • 2011
  • Vitamin D is present in two forms, ergocalciferol (vitamin $D_2$) produced by plants and cholecalciferol (vitamin $D_3$) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 $[1,25(OH)_2D]$, plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of $1,25(OH)_2D$ from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the $1{\alpha}$-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D $1{\alpha}$-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of $1,25(OH)_2D$ despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human $1{\alpha}$-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and $1{\alpha}$-hydroxylase mutations with clinical findings.

Osteomalacia and Hypophosphatemia Caused by Phosphaturic Mesenchymal Tumor Mixed Connective Tissue Variant (PMTMCT) -A Case Report- (골연화증과 저인산혈증을 유발한 인산뇨성 간엽성 종양 -증례 보고-)

  • Jeong, Jae-Yun;Kim, June-Hyuk;Lee, Sang-Hoon;Kim, Han-Soo
    • The Journal of the Korean bone and joint tumor society
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    • v.10 no.2
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    • pp.124-129
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    • 2004
  • The phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) is an extremely rare disease, and is frequently associated with oncogenic osteomalacia showing an paraneoplastic syndrome, which is characterized by phosphaturia, hypophosphatemia, normocalcemia and decreased levels of 1,25-dihydroxyvitamin D3 associated with a tumor. We experienced a 45-year-old female who had a soft tissue tumor on her right buttock causing oncogenic osteomalacia, which was satisfactorily treated by surgical excision of the mass.

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Optimization of Culture Conditions for the Bioconversion of Vitamin $D_3\;to\;1{\alpha}$,25-Dihydroxyvitamin $D_3$ Using Pseudonocardia autotrophica ID9302

  • Kang, Dae-Jung;Lee, Hong-Sub;Park, Joon-Tae;Bang, Ji-Sun;Hong, Soon-Kwang;Kim, Tae-Yong
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.5
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    • pp.408-413
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    • 2006
  • We assessed the ability of a Pseudonocardia sp. from soil samples to bioconvert vitamin $D_3$. The optimal culture conditions for the bioconversion of vitamin $D_3$ to active $1{\alpha}$,25-dihydroxyvitamin $D_3$ were investigated by varying the carbon and nitrogen sources, the metal salt concentrations, the initial pH, and the temperature. Microbial transformations were carried out with the addition of vitamin $D_3$ dissolved in ethanol. They were sampled by extraction with methanol-dichloromethane and the samples were examined by HPLC. Optimum culture conditions were found to be 0.4% yeast extract, 1% glucose, 3% starch, 1% fish meal, 0.2% NaCl, 0.01% $K_2HPO_4$, 0.2% $CaCO_3$, 0.01% NaF, and pH 7.0 at $28^{\circ}C$. The optimal timing of the addition of vitamin $D_3$ for the production of calcitriol by Pseudonocardia autotrophica ID9302 was concurrent with the inoculation of seed culture broth. Maximum calcitriol productivity and the yield of bioconversion reached a value of 10.4mg/L and 10.4% respectively on the 7th day in a 75L fementer jar under the above conditions.

Vitamin D Status and Related Biochemical Parameters of Women in Korean (한국여성의 Vitamin D 상태 및 관련 생화학적 변인에 관한 연구)

  • 문수재
    • Journal of Nutrition and Health
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    • v.29 no.7
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    • pp.758-771
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    • 1996
  • This study attempted to define reference data for the distribution of vitamin d status and to explore the relationship between vitamin D status and related biochemical indices in Korean women. The vitamin D status of 179 Korean women aged from 20 to 75 years was analyzed by using HPLC(High Pressure Liquid Chromatography). Related biochemical indices such as iPTH, alkaline phosphatase, creatinine, albumin, Ca, Mg and P were also measured. The mean serum level of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were s25.8ng/ml and 89.8pg/ml, respectively. Low 25-hydroxyvitamin D (<25nmol/L) was found in 29 subjects(16.5%). There was a significantly progressive decrease in serum 25-hydroxyvitamin D with increasing age(p<0.05). After in their, there was a dramatical reduction in 25-hydroxyvitamin D(p<0.05). It was also significant in post-menopasusal women compared with pre-menopausal women(p<0.000). Serum alkaline phosphatase levels increased significantly with age(p<0.001). Whereas serum calcium and phosphorus levels remained constant with age. Serum 250-hydroxyvitamin D was invesely related to iPTH (p<0.05) and alkaline phophatase (p<0.001).

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Anticancer Effects of Vitamin D3 Analog on Human Leukemic Cell Line(U937) and Role of Vitamin $D_3$ Analog on Immune Function of Human Peripheral Blood Lymphocytes (Human 백혈병 세포에 대한 비타민 $D_3$ 유도체의 항암효과 및 Human 임파구의 면역기능에 대한 비타민 $D_3$ 유도체의 역할)

  • 정수자
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.1
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    • pp.141-148
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    • 1998
  • This study describes the effects of 1,25-dihydroxyvitamin D3[1,25(OH)2D3, calcitriol] analog, 1,25(OH)2-16ene-23yne-D3 on proliferatin and differentiatin of the human histiocytic lymphoma cell line U937. This paper also describes the effects of 1,25(OH)2-16ene-23yne-D3 on ${\gamma}$-interferon(IFN-${\gamma}$) synthesis by phytohemagglutinin-activated peripheral blood lymphocytes(PBLs). In the present investigation, 1,25(OH2)-16ene-23yne-D3 was compared to the natural metablite of vitamin D3, 1,25(OH)2D3. 1,25(OH)2-16ene-23yne-D3 was more potent than 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of U937 cells, Its effects on inhibition of proliferation was about 30-fold more potent than 1,25(OH)2D3. On induction of differentiation as measured by nonspecific esterase (NSE) activity and morphologic change, this analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ration in Giemsa staining and the increase of adherence ability of surface. After 3 days in culture, a more significant supression of IFN-${\gamma}$ synthesis analog on supression of IFN-${\gamma}$ synthesis was a dose-dependent manner, with peak activity at 10-7M. The strong direct effects of 1,25(OH)2-16ene-23yne-D3 on cell proliferation and cell differentiation, make this compound an interesting candidate for clinical studies for several types of malignancies, and the effects on supression of IFN-${\gamma}$ synthesis provide the further evidence for a role of 1,25(OH)2-16ene-23yne-D3 in immunoregulation.

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CELLULAR RESPONSES ON ANODIZED TITANIUM DISCS COATED WITH $1{\alpha}$,25-DIHYDROXYVITAMIN D3 INCORPORATED POLY (D,L-LACTIDE-CO-GLYCOLIDE) (PLGA) NANOPARTICLES

  • Cho, Young-Jin;Heo, Seong-Joo;Koak, Jai-Young;Kim, Seong-Kyun;Lee, Joo-Hee
    • The Journal of Korean Academy of Prosthodontics
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    • v.46 no.6
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    • pp.620-627
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    • 2008
  • STATEMENT OF PROBLEM: A biochemical approach for surface modification has offered an alternative for physicochemical and morphological methods to obtain desirable bone-implant interfaces. PURPOSE: The purpose of the present study was to investigate cell responses to poly (D,L-lactide-co-glycolide) (PLGA)/$1{\alpha}$,25-(OH)$_2D_3$ coating with reference to cellular proliferation and differentiation in vitro. MATERIAL AND METHODS: 96 titanium discs were fabricated and divided into four groups. Group 1 was anodized under 300 V as control. Group 2, 3 and 4 were anodized then coated with 3 ml PLGA/$1{\alpha}$,25-(OH)$_2D_3$ solutions. Amount of the solutions were 2 ul, 20 ul and 200ul respectively. The osteoblast-like Human Osteogenic Sarcoma (HOS) cells were seeded and cultured for 1, 3 and 7 days. MTSbased cell proliferation assay and ALPase activity test were carried out. RESULTS: PLGA nanoparticles were observed as fine, smooth and round and HOS cells attached to the anodized surfaces through strand-like and sheet-like filopodia. After 3 days of culture, the dendritic filopodia were exaggerated and sheet-like cytoplasmic projections covered the coated titanium surfaces. After 3 days of culture, all of the groups showed increased cellular proliferation and the lowest proliferation rate was measured on group 2. Higher amount of incorporated $1{\alpha}$,25-(OH)$_2D_3$ (Group 3 and 4) improved cellular proliferation but the differences were not significant statistically (P > .05). But they increased the rate of ALP activities than the control group at day 3 (P < .05). CONCLUSION: Biodegradable PLGA nanoparticles incorporated with vitamin D metabolite positively affected proliferation and differentiation of cells on the anodized titanium surface.

Vitamin D Promotes Odontogenic Differentiation of Human Dental Pulp Cells via ERK Activation

  • Woo, Su-Mi;Lim, Hae-Soon;Jeong, Kyung-Yi;Kim, Seon-Mi;Kim, Won-Jae;Jung, Ji-Yeon
    • Molecules and Cells
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    • v.38 no.7
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    • pp.604-609
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    • 2015
  • The active metabolite of vitamin D such as $1{\alpha}$,25-dihydroxyvitamin ($D_3(1{\alpha},25(OH)_2D_3)$ is a well-known key regulatory factor in bone metabolism. However, little is known about the potential of vitamin D as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro. The purpose of this study was to evaluate the effect of vitamin $D_3$ metabolite, $1{\alpha},25(OH)_2D_3$, on odontoblastic differentiation in HDPCs. HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured with $1{\alpha},25(OH)_2D_3$ in the absence of differentiation-inducing factors. Treatment of HDPCs with $1{\alpha},25(OH)_2D_3$ at a concentration of 10 nM or 100 nM significantly upregulated the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein1 (DMP1), the odontogenesis-related genes. Also, $1{\alpha},25(OH)_2D_3$ enhanced the alkaline phosphatase (ALP) activity and mineralization in HDPCs. In addition, $1{\alpha},25(OH)_2D_3$ induced activation of extracellular signal-regulated kinases (ERKs), whereas the ERK inhibitor U0126 ameliorated the upregulation of DSPP and DMP1 and reduced the mineralization enhanced by $1{\alpha},25(OH)_2D_3$. These results demonstrated that $1{\alpha},25(OH)_2D_3$ promoted odontoblastic differentiation of HDPCs via modulating ERK activation.

Effect of Pyrroloquinoline Quinone on Osteoclast Generation and Activity (Pyrroloquinoline quinone이 파골세포의 생성 및 활성에 미치는 영향)

  • Ko, Seon-Yle;Han, Dong-Ho;Kim, Jung-Keun
    • Journal of Oral Medicine and Pain
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    • v.30 no.3
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    • pp.329-336
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    • 2005
  • We examined the effect of PQQ, as a scavenger of superoxide, on osteoclast-like cell formation and on mature osteoclast function. To determine whether PQQ scavenges the superoxide, nitroblue tetrazolium (NBT) staining, which is a method to detect superoxide, was performed on HD-11 cells which are a chick myelomonocytic cell line having tartrate-resistant acid phosphatase (TRAP) activity in response to 1,25-dihydroxyvitamin $D_3\;[1,25(OH)_2D_3]$. Histochemical study of TRAP was also performed on HD-11 cells. PQQ inhibited the TRAP-positive multinucleated cell formation of chicken bone marrow cells was also examined. The addition of 20 ${\mu}M$ PQQ inhibited the formation of TRAP-positive multinucleated cell. When chicken osteoclasts were cultured on dentin slices, treatment of 20 ${\mu}M$ PQQ resulted in a significant decrease in dentin resorption by osteoclasts in terms of total resorption area and number of resorption pits. The present data suggest that PQQ, possibly as a scavenger of superoxide ion, inhibits the osteoclastic differentiation and bone resorption.

Effects of a New 1,25(OH)$_2$-Vitamin $D_3$ Anglog on Proliferation and Differentiation of the Human Histiocytic Lymphoma Cell Line U937 (인체 Histiocytic Lymphoma Cell Line U937의 종식 및 분화에 대한 새로운 $1.25(OH)_2D_3$ 유도체의 효과에 관한 연구)

  • Jung, Soo-Ja;Suh, Myung-Ja;Rhu, Beung-Ho
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.23 no.3
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    • pp.443-452
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    • 1994
  • This study describes the effects of novel1, 25-dihydroxyvitamin D$_3$ analong[1,25(OH)$_2$-16ene-23yne-26, 27-F6-D$_3$] on proliferation of the human histiocytic lymphoma cell line U937 in vitro. We also examined the expression of c-myc oncogene in U937 cells was apparently inhibited to 62% and 87% of the control level after 4 days in the presence of 10-8M and 10-7 M of this analog, respectively. This compound morpholgically and functionally differentiated U937 cells to nonocyte-macrophage phenotype showing the increase of adherence ability to surface and a decrease of N/C ratio in Giemsa staining . Especially, nonspecific esterase activity which is a marker of cell differentiation to monocyte-macrophage was positive, and production of the positive stained cells increased in a dose dependent fashion . The expression of c-myc oncogene by 1, 25(OH)$_2$D$_3$ analog(10-7 M) was reduced by 60% at the mRNA level as determined by Northern blotting. The effects of this novel analog on cell proliferation and cell differentiation may open op new therapeutic strategies for human disorders such as psoriassis and may provide a tool to understand the mechanism of action of vitamin D$_3$ seco-steroids in malignancy.

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Effects of deer antler Water Extract (pilose antler of Cervus Korean TEMMINCK var. mantchuricus Sinhoe) on chondrocytes (연골세포에서 녹용약침의 효과)

  • Kim, Moo-jin;Lee, Seung-deok;Kim, Kyung-ho;Kim, Kap-sung
    • Journal of Acupuncture Research
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    • v.21 no.2
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    • pp.73-87
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    • 2004
  • 전통적인 면역억제제와 면역활동제인 녹용수용추출액(DAA)은 뼈의 재생에 있어서 중요한 역할을 한다고 여겨진다. 녹용약침이 비활성 연골세포의 분화를 야기시킬수 있는 지를 결정하기 위해, 융합된 세포 배양균을 녹용약침과 함께 24, 36, 48, 72, 120 시간동안 먼저 처리하였다. 이러한 처리후에 배양액을 10-10 ~ 10-8M 1,25-(OH)2D3를 포함하는 새로운 배양액으로 바꾸어 세포들을 추가로 24시간동안 배양했다. 앞선 연구에서 더 성숙된 활성연골세포가 이러한 Vit D3 대사산물에 반응한다는 것을 보여주었기 때문에 이러한 두 번째 처리를 선택하였다. 세포성숙에 있어서 녹용약침의 전처리 효과는 ALPase의 특이활동을 측정하는 것으로 확인하였다. 기질 단백질 합성의 변화는 35SO4 결합이 proteoglycan으로의 변화되는것과 collagen 합성을 측정함으로써 증명되었다. 비활성 연골세포가 녹용약침과 함께 120시간동안 전처리되고 다시 1,25-(OH)2D3를 추가한 처치에서 ALPase 특이활동과 collagen 합성이 농도 의존적으로 증가를 일으켰다. 그러나 proteoglycan의 생성에는 영향을 미치지 않았다. 1,25-(OH)2D3와 함께 전처리 된 비활성 연골 세포는 어떠한 전처리도 받지 않았던 비활성 연골세포처럼 반응했다. 이러한 결과는 녹용약침이 직접적으로 비활성 연골 세포를 활성 연골세포로 성숙시키는데 관여한다는 것을 알려준다. 그러므로 녹용약침은 연골내 골화과정에서 연골세포의 성숙을 조절하는데 중요한 역할을 하는 것으로 나타났다.

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