論文 - 詳細
| RRC ID | 71908 |
|---|---|
| 著者 | Yamada T, Fukasawa K, Horie T, Kadota T, Lyu J, Tokumura K, Ochiai S, Iwahashi S, Suzuki A, Park G, Ueda R, Yamamoto M, Kitao T, Shirahase H, Ochi H, Sato S, Iezaki T, Hinoi E. |
| タイトル | The role of CDK8 in mesenchymal stem cells in controlling osteoclastogenesis and bone homeostasis. |
| ジャーナル | Stem Cell Reports |
| Abstract |
Bone marrow mesenchymal stem cells (MSCs) are critical regulators of postnatal bone homeostasis. Osteoporosis is characterized by bone volume and strength deterioration, partly due to MSC dysfunction. Cyclin-dependent kinase 8 (CDK8) belongs to the transcription-related CDK family. Here, CDK8 in MSCs was identified as important for bone homeostasis. CDK8 level was increased in aged MSCs along with the association with aging-related signals. Mouse genetic studies revealed that CDK8 in MSCs plays a crucial role in bone resorption and homeostasis. Mechanistically, CDK8 in MSCs extrinsically controls osteoclastogenesis through the signal transducer and transcription 1 (STAT1)-receptor activator of the nuclear factor κ Β ligand (RANKL) axis. Moreover, aged MSCs have high osteoclastogenesis-supporting activity, partly through a CDK8-dependent manner. Finally, pharmacological inhibition of CDK8 effectively repressed MSC-dependent osteoclastogenesis and prevented ovariectomy-induced osteoclastic activation and bone loss. These findings highlight that the CDK8-STAT1-RANKL axis in MSCs could play a crucial role in bone resorption and homeostasis. |
| 巻・号 | 17(7) |
| ページ | 1576-1588 |
| 公開日 | 2022-7-12 |
| DOI | 10.1016/j.stemcr.2022.06.001 |
| PII | S2213-6711(22)00277-6 |
| PMID | 35777359 |
| PMC | PMC9287674 |
| MeSH | Animals Bone Resorption* / genetics Cell Differentiation Cyclin-Dependent Kinase 8 / genetics Cyclin-Dependent Kinase 8 / metabolism* Female Homeostasis Mesenchymal Stem Cells* / metabolism Mice NF-kappa B / metabolism Osteoclasts Osteogenesis / genetics RANK Ligand / metabolism RANK Ligand / pharmacology |
| IF | 6.032 |
| 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 | News |
| 各媒体での言及数の合計 | 2 |
| 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 | 293T(RCB2202) |