Department of Oral and Craniomaxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Laboratory for Digitized Stomatology, Research Center for Craniofacial Anomalies, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
Int J Mol Sci. 2022 Oct 13;23(20):12204. doi: 10.3390/ijms232012204.
This bedside-to-bench study aimed to systematically investigate the value of applying BMP2-loaded calcium phosphate cement (BMP2-CPC) in the restoration of large-scale alveolar bone defects. Compared to deproteinized bovine bone (DBB), BMP2-CPC was shown to be capable of inducing a favorable pattern of bone regeneration and bone remodeling accompanied by active osteoclastogenesis and optimized biomaterial resorption when applied in reconstructive periodontally accelerated osteogenic orthodontics (PAOO) surgery. To verify the regulatory role of osteoclasts in the BMP2-CPC-induced pattern of bone regeneration, in vitro and in vivo studies were designed to elucidate the underlying mechanism. Our results revealed that osteoclasts played a multifaceted role (facilitating osteogenesis, bone remodeling and biomaterial resorption) in the BMP2-CPC-induced bone regeneration. Osteoclasts contributed to the osteogenic differentiation of mesenchymal stem cells (MSCs) by secreting calcium ions, CTHRC1 and PDGF-B. Moreover, the increased osteoclasts promoted the remodeling of new bone and BMP2-CPC resorption, leading to a harmonized replacement of biomaterials with mature bone. In conclusion, the in vitro and in vivo experimental results corresponded with the clinical results and showed the optimized properties of BMP2-CPC in activating osteoclast-driven bone regeneration and remodeling, thus indicating the highly promising prospects of BMP2-CPC as an ideal therapeutic for alveolar bone defects.
本床旁到临床的研究旨在系统地研究应用负载 BMP2 的磷酸钙骨水泥（BMP2-CPC）修复大面积牙槽骨缺损的价值。与脱蛋白牛骨（DBB）相比，BMP2-CPC 在牙周加速成骨正畸（PAOO）手术中应用时，能够诱导有利的骨再生和骨重塑模式，伴随活跃的破骨细胞生成和优化的生物材料吸收。为了验证破骨细胞在 BMP2-CPC 诱导的骨再生模式中的调节作用，设计了体外和体内研究来阐明潜在的机制。我们的结果表明，破骨细胞在 BMP2-CPC 诱导的骨再生中发挥了多方面的作用（促进成骨、骨重塑和生物材料吸收）。破骨细胞通过分泌钙离子、CTHRC1 和 PDGF-B 促进间充质干细胞（MSCs）的成骨分化。此外，增加的破骨细胞促进新骨的重塑和 BMP2-CPC 的吸收，导致生物材料与成熟骨的协调替代。总之，体外和体内实验结果与临床结果一致，表明 BMP2-CPC 在激活破骨细胞驱动的骨再生和重塑方面具有优化的特性，因此表明 BMP2-CPC 作为牙槽骨缺损的理想治疗方法具有广阔的前景。
