| First Author | Martinez-Calle M | Year | 2023 |
| Journal | J Clin Invest | Volume | 133 |
| Issue | 11 | PubMed ID | 37079387 |
| Mgi Jnum | J:336552 | Mgi Id | MGI:7487921 |
| Doi | 10.1172/JCI159928 | Citation | Martinez-Calle M, et al. (2023) Transcription factor HNF4alpha2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy. J Clin Invest 133(11) |
| abstractText | 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 4alpha (HNF4alpha), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4alpha expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4alpha resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4alpha1 and Hnf4alpha2, we showed that HNF4alpha2 is the main osseous Hnf4alpha isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4alpha2 prevented bone loss in mice with CKD. Our results showed that HNF4alpha2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD. |
