• 대한치과교정학회지
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• 제27권2호
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• pp.335-347
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• 1997

교정치료시 치아이동은 치주인대세포를 매개로 골조직의 개조가 일어나는 과정으로서 골조직의 성장과 개조는 조골세포, 파골세포 및 그 전구세포의 증식, 분화 및 활성에 영향을 미치는 여러가지 전신적 인자와 국소적 인자에 의하여 조절되고 있다. 1.25-Dihydroxyvitamin $D_3$는 vitamin $D_3$의 대사물로서 경조직에 있어서 칼슘과 인산의 이동에 중요한 역할을 담당하고 있는 것으로 알려져 있으나 치주인대에 대한 1,25-Dihydroxyvitamin $D_3$의 생물학적 기능은 잘 알려져 있지 않다. 1.25-Dihydroxyvitamin $D_3$가 치주인대세포의 활성에 미치는 영향을 관찰하고자 10, 25, 50, 100ng/ml농도의 1,25 Dihydroxyvitamin $D_3$를 배양 치주인대세포에 첨가하여 배양 1, 2, 3일 후 M.T.T. 방법으로 세포의 활성을 관찰하였으며, 백서의 실험적 치아이동시 치주인대 내에 1,25-Dihydroxyvitamin $D_3$를 투여하여 12, 24, 36, 48, 72시간 및 7일 후의 조직 변화 소견을 관찰하여 다음과 같은 결과를 얻었다. 1. 10ng, 25ng/ml 농도의 1,25-Dihydroxyvitamin $D_3$를 치주인대세포에 가한 후 배양 1, 2, 3일째의 실험군 활성은 대조군과 차이가 없었다. 2. 50ng/ml 농도의 1,25-Dihydroxyvitamin $D_3$를 치주인대세포에 가한 후 배양 3일째의 활성은 대조군에 비하여 유의하게 증가되었으며 100ng/ml농도에서는 배양 2, 3일째에 유의하게 많았다. 3. 백서에 교정력을 가한 후 인장측에서의 골아세포 활성, 치주인대섬유의 파열, 모세혈관 증식은 투여후 7일까지 1.25-Dihydroxyvitamin $D_3$ 투여측과 대조측 간에 차이가 없었다. 4. 교정력을 가한 후 36시간부터 1,25-Dihydroxyvitamin $D_3$를 투여한 압박측의 파골세포 활성 및 치조골 흡수량이 증가하였다. 이상과 같은 결과로, 50-100ng/ml 농도에서 1,25-Dihydroxyvitamin $D_3$의 농도와 배양 기간에 비례하여 치주인대세포의 활성이 증가하였으며 1,25-Dihydroxyvitarnin $D_3$가 투여 36시간부터 파골세포의 활성과 그에 따른 치조골 흡수량 증가에 영향을 미쳤다고 사료된다.

• Journal of Periodontal and Implant Science
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• 제29권3호
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• pp.645-654
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• 1999

Interleukin-6(IL-6) stimulate osteoclast differentiation. $17{\beta}$-estradiol, 1,25-dihydroxyvitamin $D_3$(1,25-$(OH)_2D_3$) and interleukin-$1{\beta}$ inhibit or stimulate osteoclast differentiation by decreasing or increasing the synthesis of interleukin-6(IL-6) from stromal/osteoblastic cells, respectively. Periodontal ligament(PDL) cells reside between the alveolar bone and the cementum and have osteoblastic characteristics. To estimate the effect of $17{\beta}$-estradiol and 1,25$(OH)_2D_3$ on IL-6 production of PDL cells, PDL cells were treated with $17{\beta}$-estradiol or 1,25-$(OH)_2D_3$ in the absence or the presence of IL-$1{\beta}$. The concentration of IL-6 produced form PDL cells was determined by enzym linked immunosorbent assay(ELISA). In unstimulated PDL cells, we detected constitutive production of IL-6 at 1st and 2nd day. IL-$1{\beta}$ increased IL-6 synthesis at 1st day and 2nd day. $17{\beta}$-estradiol had no significant effect on the secretion of this cytokine, either constitutively or after stimulation with IL- $1{\beta}$(0.05 ng/ml). 1,25-$(OH)_2D_3$($10^{-8}M$) decreased not only constitutive IL-6 production but also IL-$1{\beta}$-induced IL-6 production at 2nd day. These results suggest that 1,25-$(OH)_2D_3$ may control IL-$1{\beta}$-induced osteoclast differentiation by decreasing IL-$1{\beta}$-induced IL-6 secretion of PDL cells.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.40-45
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• 2006

Several diacetoxy acetal analogues have been synthesized from santonin and assessed for their ability of inducing or enhancing the differentiation of human HL-60 leukemia cells. The compounds themselves had little effect on HL-60 cell differentiation. However, three analogues, 2a, 3a, and 5b, synergistically enhanced 1,25-dihydroxyvitamin $D_3[1,25-(OH)_2D_3]-induced$ HL-60 cell differentiation when combined with 5 nM of dihydroxyvitamin $D_3[1,25(OH)_2O_3]$, a well-known differentiation inducer. Especially, the compound 5b profoundly enhanced the $1,25-(OH)2O_3]-induced$ HL-60 cell differentiation.

• 생명과학회지
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• 제17권9호통권89호
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• pp.1191-1196
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• 2007

Eugenol은 여러가지 향신료에 있는 필수 오일의 주요 성분으로서 악성 종양 세포의 성장을 저해하고 사멸을 유도한다고 보고되었다. 본 연구에서는 eugenol이 세포 분화 유도에 관여하는지를 조사하기 위하여 HL-60 전골 수성 백혈병 세포의 분화에 미치는 eugenol의 효과를 연구하였다. HL-60 세포에 eugenol (150 ${\mu}M$)을 가했을 때 세포성장이 저해되었으며 $1,25(OH)_{2}$ vit $D_{3}$ (3 nM)와 병합처리시에는 더 큰 저해효과를 보였다. 이 때, eugenol은 $1,25(OH)_{2}$ vit $D_{3}$에 의해 유도되는 세포주기의 $G_{0}/G_{1}$단계 정지를 더욱 증가시킴을 알 수 있었다. 또한, eugenol과 $1,25(OH)_{2}$ vit $D_{3}$를 병합처리 하였을 때에는 $G_{0}/G_{1}$단계의 정지와 관련된 세포주기 조절인자인 p27 level를 상호 협동적으로 증가시켰을 뿐만 아니라 cyclin A, cdk2, cdk4 level를 감소시켰다. 또한 유세포분석실험을 통하여, CD14 (단핵세포 표지 인자)의 발현이 eugenol과 $1,25(OH)_{2}$ vit $D_{3}$를 병합처리한 세포에서 단독처리시보다 더 증가함을 알 수 있었다. 이러한 결과들은 eugenol이 $1,25(OH)_{2}$ vit $D_{3}$와 상호협동적으로 작용하여 저농도의 $1,25(OH)_{2}$ vit $D_{3}$에 의해 자극된 세포 분화 신호를 더욱 더 증대 시킴을 나타낸다. 이러한 eugenol에 의한 세포 분화 유도 작용은 암의 화학적예방 효과에 유용하게 응용될 수 있을 것으로 기대된다.

• Nutrition Research and Practice
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• 제18권1호
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• pp.1-18
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• 2024

BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)₂D₃ after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)₂D₃ during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)₂D₃ treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)₂D₃ administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)₂D₃ inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)₂D₃ treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)₂D₃ prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.

• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.169-176
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• 2010

The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($1{\alpha},25(OH)_2D_3$)-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis was investigated in an osteoblast-preosteoclast co-culture system. Serial doses of sucrose were applied as a mechanical force. These hyperosmotic stimuli significantly evoked a reduced number of $1{\alpha},25(OH)_2D_3$-induced tartrate-resistant acid phosphatase-positive multinucleated cells and $1{\alpha},25(OH)_2D_3$-induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) and Runx2 expressions were down-regulated in response to $1{\alpha},25(OH)_2D_3$. Knockdown of Runx2 inhibited $1{\alpha},25(OH)_2D_3$-induced RANKL expression in osteoblastic cells. Finally, the hyperosmotic stimulus induced the overexpression of TonEBP in osteoblastic cells. These results suggest that hyperosmolarity leads to the down-regulation of $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.

• Journal of Animal Science and Technology
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• 제56권8호
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• pp.33.1-33.8
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• 2014

Background: Sox 9 is a major marker of chondrocyte differentiation. When chondrocytes are cultured in vitro they progressively de-differentiate and this is associated with a decline in Sox 9 expression. The active form of vitamin D, 1, 25 $(OH)_2D_3$ has been shown to be protective of cartilage in both humans and animals. In this study equine articular chondrocytes were grown in culture and the effects of 1, 25 $(OH)_2D_3$ upon Sox 9 expression examined. The expression of the transient receptor potential vanilloid (TRPV) ion channels 5 and 6 in equine chondrocytes in vitro, we have previously shown, is inversely correlated with de-differentiation. The expression of these channels in response to 1, 25 $(OH)_2D_3$ administration was therefore also examined. Results: The active form of vitamin D (1, 25 $(OH)_2D_3$ when administered to cultured equine chondrocytes at two different concentrations significantly increased the expression of Sox 9 at both. In contrast 1, 25 $(OH)_2D_3$ had no significant effect upon the expression of either TRPV 5 or 6 at either the protein or the mRNA level. Conclusions: The increased expression of Sox 9, in equine articular chondrocytes in vitro, in response to the active form of vitamin D suggests that this compound could be utilized to inhibit the progressive de-differentiation that is normally observed in these cells. It is also supportive of previous studies indicating that $1{\alpha}$, 25-dihydroxyvitamin $D_3$ can have a protective effect upon cartilage in animals in vivo. The previously observed correlation between the degree of differentiation and the expression levels of TRPV 5/6 had suggested that these ion channels may have a direct involvement in, or be modulated by, the differentiation process in vitro. The data in the present study do not support this.

• 한국식품영양과학회지
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• 제27권1호
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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.

• Molecules and Cells
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• 제38권7호
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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.

• Asian-Australasian Journal of Animal Sciences
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• 제9권1호
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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.