• Title, Summary, Keyword: 1, 25-Dihydroxycholecalciferol

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Therapeutic effects of 1α,25 dihydroxycholecalciferol on osteoporotic fracture in a rat model (랫드에서 1α,25 dihydroxycholecalciferol의 골다공증성 골절 치유효과)

  • Bae, Chun-sik
    • Korean Journal of Veterinary Research
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    • v.39 no.5
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    • pp.974-985
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    • 1999
  • Osteoporosis is defined as a decrease in bone mass that leads to an increased risk of fracture. The therapeutic effect of $1{\alpha}$,25 dihydroxycholecalciferol, the hormonal form of vitamin $D_3$ that mediates calcium translation in intestine and bone, on the healing process of fracture has still been controversial. These studies were designed to understand the healing process of normal fibular fracture, the osteoporotic changes after ovariectomy, and the therapeutic effects of $1{\alpha}$,25 dihydroxycholecalciferol on the osteoporotic fracture in rats. The simple transverse fractures of rat fibulae were produced with a rotating diamond saw. The changes of the biochemical and mechanical indices of rats were investigated. The mechanical study based on bending test revealed the healing of the fibular fracture in the 5th week after simple transverse fracture. The osteoporosis impaired more the healing of osteoporotic fibular fracture than normal non-osteoporotic fibular fracture. The healing process of osteoporotic fracture was facilitated by the treatment with $1{\alpha}$,25 dihydroxycholecalciferol, however, was delayed more than the healing process of normal fracture. The bone strength based on the bending test also confirmed this tendency. The bone strengths in the 5th week after fracture of normal bone, osteoporotic bone, and $1{\alpha}$,25 dihydroxycholecalciferol-treated osteoporotic bone were 75%, 41%, and 67%, respectively, in comparison with those of intact bone. In conclusion, $1{\alpha}$,25 dihydroxycholecalciferol was effective in promoting the osteoporotic fracture healing.

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Effects of $1\alpha$, 25 Dihydroxycholecalciferol on Osteoporotic Fracture : Light Microscopic and Scanning Electron Microscopic Observation ($1\alpha$, Dihydroxycholecalciferol의 골다공증성 골절 치유효과 : 광학현미경 및 주사전자현미경적 관찰)

  • Bae, Chun-Sik
    • Applied Microscopy
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    • v.29 no.3
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    • pp.315-321
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    • 1999
  • Vitamin D is one of important factors involved in the regulation of bone metabolism. In osteoporosis, the therapeutic effect of vitamin D on the healing process of fracture has still been controversial. These studies were designed to understand the healing process of normal fibular fracture and the therapeutic effects of $1\alpha$, 25 dihydroxycholecalciferol on the osteoporotic fracture in rats. The simple transverse fractures of rat fibulae were produced with a rotating diamond saw. The histological and ultrastructural changes of rats were observed. The histological and ultrastructural studies revealed the healing of the fibular fracture in the 5th week after simple transverse fracture. The osteoporosis impaired more the healing of osteoporotic fibular fracture than normal non-osteoporotic fibular fracture. The healing process of osteoporotic fracture was facilitated by the treatment with $1\alpha$, 25 dihydroxycholecalciferol, however, was delayed more than the healing process of normal fracture. These results suggest that $1\alpha$, 25 dihydroxycholecalciferol was effective for reducing the deleterious effects of osteoporosis in fracture healing.

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1, 25(OH)$_2$-23ene-$D_3$ : Effects on Proliferation and Differentiation of U937 Cells in vitro and on Clcium Metabolism of Rat in vivo (1, 25(OH)$_2$-23ene-$D_3$ : in vitro에서 U937 세포의 증식과 분화 및 in vivo에서 쥐의 칼슘대사에 미치는 영향)

  • 정수자;서명자
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.1
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    • pp.1-9
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    • 1995
  • 1, 25(OH)2-23ene-D3 is a novel vitamine D3 analog which has a double bond between C-23 and C-24. We describe the effects of this analog on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation 1, 25(OH)2-23ene-D3 was compared to the natural metabolite of vitamin D3, 1$\alpha$, 25-dihydroxycholecalciferol[1, 25(OH)2-23ene-D3 was more potent than 1, 25(OH)2-23ene-D3 for inhibition of proliferation and induction of differentiation of U937 cells. Especially, its effect on induction of differentiation, as measured by superoxide production and nonspecific esterase(NSE) activity, was about 20-fold more potent that 1, 25(OH)2-23ene-D3. This analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability to surface. Intraperitoneal administration of 1, 25(OH)2-23ene-D3 to rats showed that the compound had at least 50 times less activity than 1, 25(OH)2-23ene-D3 in causing hypercalcemia and hypercalciuria. The strong direct effects of 1, 25(OH)2-23ene-D3 on cell proliferation and cell differentiation, coupled with its decreased activity of calcium metabolism make this compound an interesting candidate for clinical studies including patients with leukemia, as well as several skin disorders, such as psoriasis.

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Effects of 1,25 Dihydroxycholecalciferol and Ca Ionophore A23187 on Ca Transports in Bone and Bone Cells (뼈조직과 세포에서의 칼슘이동기전에 대한 1,25 dihydroxycholecaliciferol과 Ca Ionophore A23187의 영향)

  • 이선영
    • Journal of Nutrition and Health
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    • v.21 no.3
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    • pp.173-181
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    • 1988
  • Various types of evidence suggest that some changes in cellular in cellular calcium may well signal the initiation of a chain of events leading to the physiological effects of the bone resorbing agents. The effects of 1,25-dihydorxycholecalciferol, $1.25\textrm{(OH)}_2\textrm{D}_3$, Ca ionophore A23187 and calcium antagonist, diltiazem on bone resprption and the cellular transport of Ca were investigated. Bone $^{45}\textrm{Ca}$ desaturation experiment was realized in isolated heterogenous rat bone cells after equilibrating the cells with $^{45}\textrm{Ca}$. Results of $^{45}\textrm{Ca}$ desaturation experiments were analysed by fitting the $^{45}\textrm{Ca}$ desaturation curve to a model of 2 exponential terms which indicated the presence of 2 exchangeable cellular calcium pools. $1.25\textrm{(OH)}_2\textrm{D}_3$ (0.5ng/$m\ell$) induced significantly bone resorption which was decreased by the physiological dose of diltiazeme(above 5nmol/$m\ell$) although it was ineffective alone. Ionophore A23187 (0.2$\mu\textrm{g}$/$m\ell$) decreased Ca release from bone but no additivity of effect with diltiazem(20nmol/$m\ell$) was observed. $1.25\textrm{(OH)}_2\textrm{D}_3$ (0.5ng/$10^{6}$ cells) had a moderate effect on the two kinetic phases of $^{45}\textrm{Ca}$ desaturation curve and these values were normalized when diltiazeme (20nmol/$10^{6}$ cells) was added along with $1.25\textrm{(OH)}_2\textrm{D}_3$. Ionophore($0.05\mu\textrm{g}$/$10^{6}$ cells) alone increased specifically the value of the slow turnover rate which was not affected by addition of diltiazem. The hypothesis concerning the involvement of calcium in bone resorption seems in fact to be verified in case of $1.25\textrm{(OH)}_2\textrm{D}_3$ but more unsettled for Ca inophore A23187.

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Effects of Baicalin on the differentiation and activity of preosteoclasts

  • Ko, Seon-Yle
    • International Journal of Oral Biology
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    • v.34 no.2
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    • pp.81-86
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    • 2009
  • Baicalin is a flavonoid purified from the medicinal plant Scutellaria baicalensis. It has been reported that baicalin exhibits antibacterial, anti-inflammatory and analgesic effects. The present study was undertaken to determine the underlying cellular mechanisms of baicalin action in preosteoclasts. The effects of this flavonoid on preosteoclasts were determined by measuring osteoclast generation and osteoclast activity in macrophage-colony stimulating factor (M-CSF)-dependent bone marrow cells (MDBMCs) and in co-cultures of MDBMCs and osteoblasts. Osteoclast generation was assayed by measuring the number of tartrateresistant acid phosphatase (TRAP) (+) multinucleated cells after culture. Osteoclast activity was assayed by measuring the area of the resorption pit after culture. We found that osteoclast generation was induced by M-CSF and receptor activator of NF-kB ligand (RANKL), and by the 1.25-dihydroxycholecalciferol in our cultures. Baicalin decreased both osteoclast generation and activity in MDBM cultures and co-cultures indicating that it may inhibit bone resorption.

Blood Components of Diabetes and the Effect of 1,25-Dehydroxycholecalciferol on Serum Calcium Level (당뇨병 환자의 혈액성분 고찰 및 혈중-Ca 농도에 대한 1,25-Dehydroxycholecalciferol의 급여 효과)

  • Park, M.A.;Lim, S.J.;Yu, J.Y.
    • Journal of Nutrition and Health
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    • v.17 no.4
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    • pp.273-280
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    • 1984
  • The blood components of diabetic patients who visited S- hospital in seoul from January 1982 to June 1983 were compared with the reference levels. Hemoglobin and hematocrit levels of diabetic patients were significantly lower than the reference. The diabetic patients showed 2-3 times higher levels of fasting blood glucose and postprandial -2 hours blood sugar. Levels of blood urine nitrogen and creatine were also significantly higher in the diabetes mellitus and the levels of potassium sodium and chlorine showed no differences although these were decreased gradually in older patients. Lower serum calcium levels were seen in the diabetic patients and this change was more significant at the ages higher than 40. The effect of an active vitamin D on serum-Ca level in diabetic patients was studied in comparison to that of non- diabetic persons. The serum calcium levels were slightly increased in control and insulin- dependent diabetic patients after a week- intake of 1,000mg calcium a day, while the intake of 1,25-dihydroxycholecalciferol ( 1,000 IU per day ) did not increase the serum calcium levels of these groups. Insulin - independent diabetic patients showed the rather lower serum calcium levels after a week- intake of 1,000mg calcium per day. However, the levels were increased after 2-weeks intake of the calcium and a week-in-take of the active vitamin D(1,000 IU/day ). This effect of vitamin D was seen in the groups with lower intake of calcium(500mg/day ) but not in the groups with 1,000mg calcium intake a day.

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TRIIODTHYRONINE (T3) ENHANCES THE STIMULATORY EFFECT OF 1, 25-DIHYDROXYVITAMIN D3 ON CALBINDIN-D28k mRNA EXPRESSION IN THE KIDNEY AND INTESTINE BUT NOT IN CEREBELLUM OF THE CHICK

  • Sechman, A.;Shimada, K.;Saito, N.;Ieda, T.;Ono, T.
    • Asian-Australasian Journal of Animal Sciences
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    • v.9 no.1
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    • pp.37-44
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    • 1996
  • The present study was conducted to investigate the role of thyroid hormones in the regulation of gene expression of calbindin-$D_{28k}$ (CaBP-D28K) in the chicken. By employing slot blot and RIA analyses, levels of CABP-D28K mRNA and CaBP-D28K protein in the intestine, kidney, cerebellum and liver were measured 6 and 12 h after i.m. injection of 1, 25-dihydroxyvitamin $D_3$ [1, 25 $(OH)_2D_3$; 250 ng/chick] and 3, 5, 3'-triiodothyronine ($T_3$; 500 ng/chick) in one-day-old chicks. The abundant messages of CaBP-D28K mRNA were detected in the intestine, kidney and cerebellum while there was little message in the liver. After 1, 25 $(OH)_2D_3$ treatment (6 + 12 hours), levels of CaBP-D28K mRNA increased in the intestine, but there was no change in the mRNA levels in the kidney and cerebellum. Although $T_3$ alone had no effect on CaBP-D28K mRNA levels, simultaneous administration of $T_3$ enhanced the 1, 25 $(OH)_2D_3$ effect of levels of CaBP-D28K mRNA in the intestine both 6 and 12 h post-treatment, and in the kidney 12 h post-treatment. At a protein level, co-treatment with 1, 25 $(OH)_2D_3$ and $T_3$ elicited a significant increase in CaBP-D28K expression in the intestine 12 h post-treatment, as compared to treatment with only 1, 25 $(OH)_2D_3$, whereas no differences were observed in the CaBP-D28K protein levels in the kidney and cerebellum. These results suggest that thyroid hormones may play a synergistic role with 1, 25 $(OH)_2D_3$ for CaBP-D28K gene expression in the intestine and kidney in chicks.

Effects of Leptin on Osteoclast Generation and Activity

  • Ko, Seon-Yle;Cho, Sang-Rae;Kim, Se-Won;Kim, Jung-Keun
    • International Journal of Oral Biology
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    • v.30 no.2
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    • pp.47-57
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    • 2005
  • Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. Several results suggest that leptin is important mediators of bone metabolism. The present study was undertaken to determine the effects of leptin on anti-osteoclastogenesis using murine precursors cultured on Ca-P coated plates and on the production of osteoprotegerin (OPG) in osteoblastic cells. Additionally, this study examined the possible involvement of prostaglandin $E_2\;(PGE_2)$/protein kinase C (PKC)-mediated signals on the effect of leptin on anti-osteoclastogenesis to various culture systems of osteoclast precursors. Osteoclast generation was determined by counting tartrate-resistant acid phosphatase positive [TRAP (+)] multinucleated cells (MNCs). Osteoclastic activity was determined by measuring area of resorption pits formed by osteoclasts on Ca-P coated plate. The number of 1,25-dihydroxycholecalciferol $(1,25[OH]_2D_3)$- or $PGE_2$-induced TRAP (+) MNCs in the mouse bone marrow cell culture decreased significantly after treatment with leptin. The number of receptor activator of NF-kB ligand (RANKL)-induced TRAP (+) MNCs in M-CSF dependent bone marrow macrophage (MDBM) cell or RAW264.7 cell culture decreased significantly with leptin treatment. Indomethacin inhibited osteoclast generation induced by $1,25[OH]_2D_3$ and dexamethasone, however, no significant differences were found in the leptin treated group when compared to the corresponding indomethacin group. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, inhibited osteoclast generation induced by $1,25[OH]_2D_3$. The number of TRAP (+) MNCs decreased significantly with treatment by PMA at concentrations of 0.01 and $0.1{\mu}M$ in culture. Leptin inhibited PMA-mediated osteoclast generation. Isoquinoline-5-sulfonic 2-methyl-1-piperazide dihydrochloride (H7) had no effect on osteoclast generation induced by $1,25[OH]_2D_3$. Cell culture treatment with leptin resulted in no significant differences in osteoclast generation compared to the corresponding H7 group. Indomethacin showed no significant effect on TRAP (+) MNCs formation from the RAW264.7 cell line. PMA inhibited TRAP (+) MNCs formation induced by RANKL in the RAW264.7 cell culture. H7 had no effect on osteoclast generation from the RAW264.7 cell line. There was no difference compared with the corresponding control group after treatment with leptin. $1,25[OH]_2D_3$- or $PGE_2$-induced osteoclastic activity decreased significantly with leptin treatment at a concentration of 100 ng/ml in mouse bone marrow cell culture. Indomethacin, PMA, and H7 significantly inhibited osteoclastic activity induced by $1,25[OH]_2D_3$ in mouse bone marrow cell culture. No significant differences were found between the leptin treated group and the corresponding control group. The secretion of OPG, a substance known to inhibit osteoclast formation, was detected from the osteoblasts. Treatment by leptin resulted in significant increases in OPG secretion by osteoblastic cells. Taken these results, leptin may be an important regulatory cytokines within the bone marrow microenvironment.

Vitamin D Receptor Gene TaqI, BsmI and FokI Polymorphisms in Korean Patients with Tuberculosis

  • Kang, Tae-Jin;Jin, Song-Hou;Yeum, Chung-Eun;Lee, Seong-Beom;Kim, Chi-Hong;Lee, Sang-Haak;Kim, Kwan-Hyoung;Shin, Eun-Soon;Chae, Gue-Tae
    • IMMUNE NETWORK
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    • v.11 no.5
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    • pp.253-257
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    • 2011
  • Background: The active metabolite (1, 25- dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. Methods: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. Results: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). Conclusion: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.