論文 - 詳細
| RRC ID | 85972 |
|---|---|
| 著者 | Kitazawa R, Haraguchi R, Kitazawa S. |
| タイトル | A variant form of receptor activator of nuclear factor-κB functions as an osteoprotegerin mimic in bone and cardiac development. |
| ジャーナル | Sci Rep |
| Abstract |
Bone remodeling is tightly regulated by the RANK-RANKL-OPG axis to maintain skeletal integrity. We previously identified a RANK splicing variant, vRANK, which encodes a truncated protein that inhibits osteoclastogenesis and promotes apoptosis. This study examined the regulatory mechanisms of vRANK expression in vitro and its physiological role in vivo using transgenic mice with forced vRANK expression in the monocyte-macrophage lineage and in a systemic manner. In vitro, PMA and TGF-β1 specifically induced vRANK expression, which was completely suppressed by U0126, a MEK1/2 inhibitor, and significantly reduced by Sam68 knockdown, indicating its involvement in RNA splicing regulation. In vivo, RANK-Cre-driven vRANK expression had no skeletal impact, whereas LysM-Cre-driven expression resulted in increased bone mass and suppressed osteoclastogenesis. However, systemic overexpression of vRANK (CAG-CreER) caused perinatal lethality, severe cardiac fibrosis, and immune dysfunction. Notably, myocardial fibrosis in vRANK-overexpressing mice correlated with TGF-β1 upregulation in fibrotic foci, suggesting a pathological feedback loop exacerbating fibrosis. These findings suggest that vRANK functions similarly to OPG in inhibiting osteoclastogenesis while also potentially playing a role in cardiac remodeling and immune regulation. |
| 巻・号 | 15(1) |
| ページ | 27919 |
| 公開日 | 2025-7-31 |
| DOI | 10.1038/s41598-025-13314-7 |
| PII | 10.1038/s41598-025-13314-7 |
| PMID | 40745459 |
| PMC | PMC12314122 |
| MeSH | Animals Bone Development* / genetics Bone and Bones* / metabolism Heart* / embryology Heart* / growth & development Mice Mice, Transgenic Myocardium / metabolism Myocardium / pathology Osteoclasts / metabolism Osteogenesis / genetics Osteoprotegerin* / genetics Osteoprotegerin* / metabolism RANK Ligand / metabolism Receptor Activator of Nuclear Factor-kappa B* / genetics Receptor Activator of Nuclear Factor-kappa B* / metabolism Transforming Growth Factor beta1 / metabolism |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 1 |
| 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 | RAW 264(RCB0535) |