論文 - 詳細
| RRC ID | 54686 |
|---|---|
| 著者 | Nguyen HT, Ono M, Oida Y, Hara ES, Komori T, Akiyama K, Nguyen HTT, Aung KT, Pham HT, Tosa I, Takarada T, Matsuo K, Mizoguchi T, Oohashi T, Kuboki T. |
| タイトル | Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment. |
| ジャーナル | J Bone Miner Res |
| Abstract |
Bone morphogenetic protein 2 (BMP-2) is widely known as a potent growth factor that promotes bone formation. However, an increasing number of studies have demonstrated side effects of BMP-2 therapy. A deeper understanding of the effect of BMP-2 on cells other than those involved directly in bone remodeling is of fundamental importance to promote a more effective delivery of BMP-2 to patients. In this study, we aimed to investigate the effect of BMP-2 in the marrow environment. First, BMP-2 adsorbed onto titanium implants was delivered at the tooth extraction socket (marrow-absent site) or in the mandible marrow of beagle dogs. BMP-2 could induce marked bone formation around the implant at the tooth extraction socket. Surprisingly, however, no bone formation was observed in the BMP-2-coated titanium implants inserted in the mandible marrow. In C57BL/6 mice, BMP-2 adsorbed in freeze-dried collagen pellets could induce bone formation in marrow-absent calvarial bone. However, similar to the canine model, BMP-2 could not induce bone formation in the femur marrow. Analysis of osteoblast differentiation using Col1a1(2.3)-GFP transgenic mice revealed a scarce number of osteoblasts in BMP-2-treated femurs, whereas in the control group, osteoblasts were abundant. Ablation of femur marrow recovered the BMP-2 ability to induce bone formation. In vitro experiments analyzing luciferase activity of C2C12 cells with the BMP-responsive element and alkaline phosphatase activity of MC3T3-E1 osteoblasts further revealed that bone marrow cells inhibit the BMP-2 effect on osteoblasts by direct cell-cell contact. Collectively, these results showed that the effect of BMP-2 in inducing bone formation is remarkably repressed by marrow cells via direct cell-cell contact with osteoblasts; this opens new perspectives on the clarification of the side-effects associated with BMP-2 application. © 2018 American Society for Bone and Mineral Research. |
| 巻・号 | 34(2) |
| ページ | 327-332 |
| 公開日 | 2019-2-1 |
| DOI | 10.1002/jbmr.3598 |
| PMID | 30352125 |
| MeSH | Animals Bone Marrow Cells / metabolism* Bone Marrow Cells / pathology Bone Morphogenetic Protein 2* / chemistry Bone Morphogenetic Protein 2* / pharmacology Cellular Microenvironment / drug effects* Cellular Microenvironment / genetics Coated Materials, Biocompatible* / chemistry Coated Materials, Biocompatible* / pharmacology Dogs Female Femur / metabolism Femur / pathology Humans Mice Mice, Transgenic Osteoblasts / metabolism* Osteoblasts / pathology Osteogenesis / drug effects* Osteogenesis / genetics Titanium* / chemistry Titanium* / pharmacology |
| IF | 5.711 |
| 引用数 | 2 |
| 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 | 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 | MC3T3-E1(RCB1126) |