論文 - 詳細
| RRC ID | 65563 |
|---|---|
| 著者 | Morimoto A, Kikuta J, Nishikawa K, Sudo T, Uenaka M, Furuya M, Hasegawa T, Hashimoto K, Tsukazaki H, Seno S, Nakamura A, Okuzaki D, Sugihara F, Ninomiya A, Yoshimura T, Takao-Kawabata R, Matsuda H, Ishii M. |
| タイトル | SLPI is a critical mediator that controls PTH-induced bone formation. |
| ジャーナル | Nat Commun |
| Abstract |
Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast-osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism. |
| 巻・号 | 12(1) |
| ページ | 2136 |
| 公開日 | 2021-4-9 |
| DOI | 10.1038/s41467-021-22402-x |
| PII | 10.1038/s41467-021-22402-x |
| PMID | 33837198 |
| PMC | PMC8035405 |
| MeSH | Animals Bone Resorption / drug therapy* Bone Resorption / pathology Cell Differentiation / drug effects Cell Differentiation / physiology Cell Line Disease Models, Animal Female Femur / cytology Femur / diagnostic imaging Femur / drug effects Femur / pathology Humans Male Mice Mice, Knockout Osteoblasts / drug effects Osteoblasts / metabolism Osteoclasts / drug effects Osteoclasts / metabolism Osteogenesis / drug effects Osteogenesis / physiology* Parathyroid Hormone / administration & dosage* Primary Cell Culture RNA-Seq Secretory Leukocyte Peptidase Inhibitor / genetics Secretory Leukocyte Peptidase Inhibitor / metabolism* Up-Regulation / drug effects X-Ray Microtomography |
| IF | 12.121 |
| 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 | 12 |
| 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 | |
| 遺伝子材料 | CSII-EF-MCS (RDB04378) |