Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.
Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.
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DOI：
10.1172/jci159928
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发表时间：
2023-06-01
影响因子：
15.9
通讯作者：
Martin, Aline
中科院分区：
文献类型：
--
作者：
Martinez-Calle, Marta;Courbon, Guillaume;Hunt-Tobey, Bridget;Francis, Connor;Spindler, Jadeah;Wang, Xueyan;Reis, Luciene M. dos;Martins, Carolina S. W.;Salusky, Isidro B.;Malluche, Hartmut;Nickolas, Thomas L.;Moyses, Rosa M. A.;David, Valentin;Martin, Aline
Renal osteodystrophy (ROD) is a disorder of bone metabolism that affects virtually all patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes including fractures, cardiovascular events, and death. In this study, we showed that hepatocyte nuclear factor 4α (HNF4α), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4α expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4α resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4α1 and Hnf4α2, we showed that HNF4α2 is the main osseous Hnf4α isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4α2 prevented bone loss in mice with CKD. Our results showed that HNF4α2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD.
慢性肾脏疾病中冠状动脉钙化的候选基因关联研究：CRIC研究的发现（慢性肾功能不全队列）。
影响因子：
24
作者：
Ferguson, Jane F.;Matthews, Gregory J.;Townsend, Raymond R.;Raj, Dominic S.;Kanetsky, Peter A.;Budoff, Matthew;Fischer, Michael J.;Rosas, Sylvia E.;Kanthety, Radhika;Rahman, Mahboob;Master, Stephen R.;Qasim, Atif;Li, Mingyao;Mehta, Nehal N.;Shen, Haiqing;Mitchell, Braxton D.;O'Connell, Jeffrey R.;Shuldiner, Alan R.;Ho, Weang Kee;Young, Robin;Rasheed, Asif;Danesh, John;He, Jiang;Kusek, John W.;Ojo, Akinlolu O.;Flack, John;Go, Alan S.;Gadegbeku, Crystal A.;Wright, Jackson T., Jr.;Saleheen, Danish;Feldman, Harold I.;Rader, Daniel J.;Foulkes, Andrea S.;Reilly, Muredach P.
通讯作者：
Reilly, Muredach P.
影响因子：
8.2
作者：
Jafar-Mohammadi, B.;Groves, C. J.;Gjesing, A. P.;Herrera, B. M.;Winckler, W.;Stringham, H. M.;Morris, A. P.;Lauritzen, T.;Doney, A. S. F.;Morris, A. D.;Weedon, M. N.;Swift, A. J.;Kuusisto, J.;Laakso, M.;Altshuler, D.;Hattersley, A. T.;Collins, F. S.;Boehnke, M.;Hansen, T.;Pedersen, O.;Palmer, C. N. A.;Frayling, T. M.;Gloyn, A. L.;McCarthy, M. I.
通讯作者：
McCarthy, M. I.