| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
