骨形态发生蛋白2
破骨细胞
成骨细胞
细胞生物学
离体
骨免疫学
免疫系统
骨吸收
材料科学
癌症研究
化学
医学
免疫学
生物
内科学
受体
体外
生物化学
兰克尔
激活剂(遗传学)
作者
Yamei Xu,Yao Yang,Ziyi Hua,Shuang Li,Zhenyu Yang,Qianzi Liu,Gang Fu,Ping Ji,Qingqing Wu
出处
期刊:Biomaterials
[Elsevier]
日期:2021-08-01
卷期号:275: 120890-120890
被引量:21
标识
DOI:10.1016/j.biomaterials.2021.120890
摘要
BMP2 antibody is proposed as a promising replacement for rhBMP2 in bone tissue engineering. Although studies have demonstrated its osteoinductive efficacy, the underlying osteogenic mechanism and adverse reactions of specific BMP2 antibody are not clarified yet, making it difficult to optimize the antibody for future application. By establishing BMP2 immune complexes (BMP2-ICs) ex vivo, we were able to introduce BMP2-ICs directly in vivo and found that BMP2-ICs promoted bone formation while suppressing osteoclastogenesis. However, ex vivo osteoclastogenic assays showed that BMP2-ICs promoted osteoclastogenesis by binding FcγR and activating PLCγ2 phosphorylation. Given that BMP2-ICs react with osteoblast and osteoclast lineage cells by the conjugated BMP2 domain and the Fc domain respectively, we introduced BMP2-ICs into coculture system of the two lineage cells and found that BMP2-ICs promoted osteogenesis while suppressing osteoclastogenesis by facilitating osteoblast-osteoclast contact and activating the EphrinB2-EphB4 signaling. This bidirectional function of BMP2-ICs was reproduced in the cranial bone resorption model, where osteoblast and osteoclast lineage cells co-localized. This study excluded the hidden problem of osteoclast overactivation that usually comes with rhBMP2 and clarified the first evidence of the mechanism of antibody-mediated bone regeneration, suggesting BMP2-ICs may present a promising therapy for bone diseases related with disrupted osteoclast-osteoblast interaction.
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