論文 - 詳細
| RRC ID | 53918 |
|---|---|
| 著者 | Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H. |
| タイトル | Coupling of bone resorption and formation by RANKL reverse signalling. |
| ジャーナル | Nature |
| Abstract |
Receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) binds RANK on the surface of osteoclast precursors to trigger osteoclastogenesis. Recent studies have indicated that osteocytic RANKL has an important role in osteoclastogenesis during bone remodelling; however, the role of osteoblastic RANKL remains unclear. Here we show that vesicular RANK, which is secreted from the maturing osteoclasts, binds osteoblastic RANKL and promotes bone formation by triggering RANKL reverse signalling, which activates Runt-related transcription factor 2 (Runx2). The proline-rich motif in the RANKL cytoplasmic tail is required for reverse signalling, and a RANKL(Pro29Ala) point mutation reduces activation of the reverse signalling pathway. The coupling of bone resorption and formation is disrupted in RANKL(Pro29Ala) mutant mice, indicating that osteoblastic RANKL functions as a coupling signal acceptor that recognizes vesicular RANK. RANKL reverse signalling is therefore a potential pharmacological target for avoiding the reduced bone formation associated with inhibition of osteoclastogenesis. |
| 巻・号 | 561(7722) |
| ページ | 195-200 |
| 公開日 | 2018-9-1 |
| DOI | 10.1038/s41586-018-0482-7 |
| PII | 10.1038/s41586-018-0482-7 |
| PMID | 30185903 |
| MeSH | Amino Acid Substitution Animals Bone Resorption / metabolism* Cell Differentiation Core Binding Factor Alpha 1 Subunit / metabolism Cross-Linking Reagents / chemistry Cytoplasmic Vesicles / metabolism Female Male Mice Mice, Inbred C57BL Osteoblasts / cytology Osteoblasts / metabolism Osteoclasts / cytology Osteoclasts / metabolism Osteogenesis* RANK Ligand / chemistry RANK Ligand / deficiency RANK Ligand / genetics RANK Ligand / metabolism* Receptor Activator of Nuclear Factor-kappa B / genetics Receptor Activator of Nuclear Factor-kappa B / metabolism Signal Transduction* |
| IF | 42.779 |
| 引用数 | 78 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 90 |
| 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 | ST2(RCB0224) RAW 264(RCB0535) |