論文 - 詳細
| RRC ID | 27899 |
|---|---|
| 著者 | Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, Kikuchi Y, Takada I, Kato S, Kani S, Nishita M, Marumo K, Martin TJ, Minami Y, Takahashi N. |
| タイトル | Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. |
| ジャーナル | Nat Med |
| Abstract |
The signaling molecule Wnt regulates bone homeostasis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. Impairment of canonical Wnt signaling causes bone loss in arthritis and osteoporosis; however, it is unclear how noncanonical Wnt signaling regulates bone resorption. Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor (Ror) proteins. We showed that Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhanced osteoclastogenesis. Osteoblast-lineage cells expressed Wnt5a, whereas osteoclast precursors expressed Ror2. Mice deficient in either Wnt5a or Ror2, and those with either osteoclast precursor-specific Ror2 deficiency or osteoblast-lineage cell-specific Wnt5a deficiency showed impaired osteoclastogenesis. Wnt5a-Ror2 signals enhanced receptor activator of nuclear factor-κB (RANK) expression in osteoclast precursors by activating JNK and recruiting c-Jun on the promoter of the gene encoding RANK, thereby enhancing RANK ligand (RANKL)-induced osteoclastogenesis. A soluble form of Ror2 acted as a decoy receptor of Wnt5a and abrogated bone destruction in mouse arthritis models. Our results suggest that the Wnt5a-Ror2 pathway is crucial for osteoclastogenesis in physiological and pathological environments and represents a therapeutic target for bone diseases, including arthritis. |
| 巻・号 | 18(3) |
| ページ | 405-12 |
| 公開日 | 2012-2-19 |
| DOI | 10.1038/nm.2653 |
| PII | nm.2653 |
| PMID | 22344299 |
| MeSH | Animals Arthritis / metabolism Bone Diseases / metabolism Cell Lineage Gene Expression Regulation MAP Kinase Kinase 4 / metabolism Mice Osteoblasts / cytology Osteoblasts / metabolism* Osteoclasts / cytology Osteoclasts / metabolism* Promoter Regions, Genetic Proto-Oncogene Proteins c-jun / genetics Proto-Oncogene Proteins c-jun / metabolism Receptor Activator of Nuclear Factor-kappa B / genetics Receptor Activator of Nuclear Factor-kappa B / metabolism Receptor Tyrosine Kinase-like Orphan Receptors / deficiency Receptor Tyrosine Kinase-like Orphan Receptors / genetics Receptor Tyrosine Kinase-like Orphan Receptors / metabolism* Skull / cytology Skull / growth & development Wnt Proteins / deficiency Wnt Proteins / genetics Wnt Proteins / metabolism* Wnt Signaling Pathway* Wnt-5a Protein X-Ray Microtomography |
| IF | 36.13 |
| 引用数 | 244 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 16 |
| 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 | |
| 実験動物マウス | RBRC01834 RBRC02096 |