論文 - 詳細
| RRC ID | 17608 |
|---|---|
| 著者 | Kriebitzsch C, Verlinden L, Eelen G, van Schoor NM, Swart K, Lips P, Meyer MB, Pike JW, Boonen S, Carlberg C, Vitvitsky V, Bouillon R, Banerjee R, Verstuyf A. |
| タイトル | 1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine β-synthase. |
| ジャーナル | J Bone Miner Res |
| Abstract |
High homocysteine (HCY) levels are a risk factor for osteoporotic fracture. Furthermore, bone quality and strength are compromised by elevated HCY owing to its negative impact on collagen maturation. HCY is cleared by cystathionine β-synthase (CBS), the first enzyme in the transsulfuration pathway. CBS converts HCY to cystathionine, thereby committing it to cysteine synthesis. A microarray experiment on MC3T3-E1 murine preosteoblasts treated with 1,25-dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] revealed a cluster of genes including the cbs gene, of which the transcription was rapidly and strongly induced by 1,25(OH)(2) D(3) . Quantitative real-time PCR and Western blot analysis confirmed higher levels of cbs mRNA and protein after 1,25(OH)(2) D(3) treatment in murine and human cells. Moreover, measurement of CBS enzyme activity and quantitative measurements of HCY, cystathionine, and cysteine concentrations were consistent with elevated transsulfuration activity in 1,25(OH)(2) D(3) -treated cells. The importance of a functional vitamin D receptor (VDR) for transcriptional regulation of cbs was shown in primary murine VDR knockout osteoblasts, in which upregulation of cbs in response to 1,25(OH)(2) D(3) was abolished. Chromatin immunoprecipitation on chip and transfection studies revealed a functional vitamin D response element in the second intron of cbs. To further explore the potential clinical relevance of our ex vivo findings, human data from the Longitudinal Aging Study Amsterdam suggested a correlation between vitamin D status [25(OH)D(3) levels] and HCY levels. In conclusion, this study showed that cbs is a primary 1,25(OH)(2) D(3) target gene which renders HCY metabolism responsive to 1,25(OH)(2) D(3). |
| 巻・号 | 26(12) |
| ページ | 2991-3000 |
| 公開日 | 2011-12-1 |
| DOI | 10.1002/jbmr.493 |
| PMID | 21898591 |
| PMC | PMC3222742 |
| MeSH | Aged Aged, 80 and over Amino Acids / metabolism Animals Blotting, Western Cell Line Cystathionine beta-Synthase / genetics* Cystathionine beta-Synthase / metabolism Gene Expression Regulation, Enzymologic / drug effects* Homocysteine / metabolism* Humans Metabolic Networks and Pathways / drug effects Mice Mice, Inbred C57BL Middle Aged Osteoblasts / cytology Osteoblasts / drug effects* Osteoblasts / enzymology* Protein Binding / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Calcitriol / metabolism Response Elements / genetics Transcriptional Activation / drug effects Transcriptional Activation / genetics Up-Regulation / drug effects Vitamin D / analogs & derivatives* Vitamin D / blood Vitamin D / pharmacology |
| IF | 5.854 |
| 引用数 | 45 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-E1(RCB1126) Saos-2(RCB0428) |