Freire Marcelo, Choi Jeong-Ho, Nguyen Anthony, Chee Young Deok, Kook Joong-Ki, You Hyung-Keun, Zadeh Homayoun H
Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA, USA ; Department of Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Department of Orthodontics, School of Dentistry, Seoul National University, Jongno-gu, Seoul 110-749, Republic of Korea.
Biomed Res Int. 2015;2015:628769. doi: 10.1155/2015/628769. Epub 2015 Jan 29.
Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models.
内源性分子和细胞介质调节组织修复和再生。我们最近将抗体介导的骨再生（AMOR）描述为一种在大鼠颅骨缺损中进行骨生物工程的新策略。这需要应用能够在体内捕获内源性成骨骨形态发生蛋白（BMP-2、BMP-4和BMP-7）的抗BMP-2抗体。本研究旨在探讨AMOR在其他动物模型中的可行性。为此，我们检测了一组固定在可吸收胶原海绵（ACS）上的抗BMP-2单克隆抗体（mAb）和一种多克隆抗体在兔颅骨临界尺寸缺损中介导骨再生的效果。6周后，通过微型计算机断层扫描成像、组织学和组织形态计量学分析证实了新骨形成。只有某些抗BMP-2 mAb克隆在体内介导了显著的骨再生，这表明抗BMP-2 mAb反应的表位对AMOR至关重要。在缺损内观察到BMP-2蛋白的定位增加和骨钙素的表达增加，这表明内源性BMP-2的积累和/或在通过AMOR进行骨修复的部位BMP-2蛋白的新生表达增加。考虑到将这种治疗策略应用于人类的最终目标，需要进行临床前研究以证明AMOR在逐渐增大的动物模型中的可行性。
