• Applied Microscopy
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• 제32권3호
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• pp.223-230
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• 2002

Sprague-Dawley rat에 complete Freund's adjuvant (CFA)를 투여하여 유발한 골다공증에 미치는 $1{\alpha}$, 25 dihydroxyvitamin $D_3\;(Vit\;D_3)$의 효과를 알아보기 위하여 실험동물을 정상 대조군, CFA 투여 대조군, CFA 투여후 $1{\alpha}$, 25 dihydroxyvitamin $D_3\;0.01{\mu}g/kg$ 투여군 (Vit $D_{3}L$) 및 $0.1{\mu}g/kg$ 투여군(Vit $D_{3}H$)으로 분류하여 경구로 3주간 투여하였다. 골다공증의 억제 효과를 알아보기 위하여 골밀도와 골함유량의 변화 및 주사전자현미경적 소견을 관찰한 결과 다음과 같은 결론을 얻었다. 골밀도와 골함유량은 $1{\alpha}$, 25 dihydroxyvitamin $D_3$ 투여용량과 부위에 따라 차이가 있었는데 Vit $D_3$ 투여군이 CFA 투여 대조군과 비교하여 골밀도와 골함유량이 증가하였으며 Vit $D_{3}H$군이 Vit $D_{3}L$군보다 좀 더 효과적이었다. 대퇴골의 주사전자현미경적 소견은 Vit $D_3$ 투여군의 골피질과 골소주의 손상이 CFA 투여 대조군보다 억제되었음을 볼 수 있었으며 Vit $D_{3}H$ 투여군이 Vit $D_{3}L$ 투여군보다 좀 더 효과적이었다. 이상의 결과를 종합해 보면 $1{\alpha}$, 25 dihydroxyvitamin $D_3$의 투여는 CFA에 의해 유발된 rat의 골다공증 모델에서 골다공증의 진행을 억제하였고 Vit $D_{3}H$ 투여군이 Vit $D_{3}L$ 투여군보다 좀 더 효과적이었다.

• Journal of Periodontal and Implant Science
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• 제30권1호
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• pp.39-52
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• 2000

Polypeptide growth factor belong to a class of potent biologic mediator which regulate cell differentiation, proliferation, migration and metabolism. 1,25-dihydroxyvitamin $D_3$ decrease cell proliferation, and stimulate alkaline phosphatase activity which express in osteoblast during cell differentiation period. IGF-I is known to stimulate cell proliferation and differentiation too. 1,25-dihydroxyvitamin $D_3$ is known to increase IGF-I binding sites and IGF binding protein which inhibite the effect of IGF. The purpose of this study is to evaluate potential role of IGF-I as mediator that control the action of 1,25-dihydroxyvitamin $D_3$. MC3T3-E1 cell were seeded $5{\times}10^5/ml$ at 100mm culture plate in ${\alpha}-MEM$ containing 10% fetal bovine serum. After 48 hour incubation period, medium were changed ${\alpha}-MEM$ containing 5% fetal bovine serum. After 24 hours, $10^{-9}M$ 1,25-dihydroxyvitamin $D_3$ added. Total mRNA was extracted at 0, 6, 24, 48, 72 hour. PRPCR method was programed for the detection of IGF-I mRNA. In the both groups of 1,25-dihydroxy vitamin $D_3$ treated and control, alternative splicing form of IGF-I, IGF-IA and IGF-IB were expressed. In the 1,25-dihydroxyvitamin $D_3$ treated group, IGF-I mRNA expression was matained until 24 hour, there after expression was decresed. MC3T3-E1 cell were seeded $2.5{\times}10^4/ml$ at 24well plate in ${\alpha}-MEM$ containing 10% fetal bovine serum. After 48 hour incubation period, medium were changed ${\alpha}-MEM$ containing 3% fetal bovine serum. After 24 hours, $10^{-9}M$ 1,25-dihydroxyvitamin $D_3$ and 10 ng/ml IGF-I were added separately or together. Cell were cultured for 1 and 3 days, $2{\mu}Ci/ml\;[^3H]$ -thymidine was added for the last 24h of culture of each days. ${[^3H]}$-thymidine incorporation in to DNA was measured and expressed counter per minute(CPM). DNA synthetic activity was significantly decreased by 1,25-dihydroxyvitamin $D_3$ both at 1 day and 3 day, and in the combination group of 1,25-dihydroxyvitamin $D_3$ and IGF-I, DNA synthetic activity was also decreased both at 1 day and 3 days. IGF-I did not affect the DNA synthetic activity compared to control group both at 1 day and 3 day. From the above results, 1,25-dihydroxyvitamin $D_3$ was potent inhibitor of cell proliferaton in MC3T3-E1 cells. It assumed that the effect of 1,25-dihydroxyvitamin $D_3$ on osteoblast proliferation may be mediated in part by decreased level of IGF-I.

• Archives of Pharmacal Research
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• 제23권3호
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• pp.206-210
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• 2000

A new series of phosphonate side chain analogues of 1$\alpha$,25-dihydroxyvitamin $D_3$ (1) have been synthesized. Antiproliferative activities of theses analogues (8a,b and 9a,b) using human keratinocyte cell shows that analogues which have natural A-ring show higher activity than unnatural A-ring series and almost equally active to 1 $\alpha$,25-Dihydroxyvitamin $D_3$(1) at 1 $\mu$M level.

• 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.

• 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.

• 한국영양학회:학술대회논문집
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• 한국영양학회 1999년도 춘계학술대회 초록
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• pp.41-42
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• 1999

• 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.

• Clinical and Experimental Pediatrics
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• 제54권2호
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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.

• 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.

• 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.