Wang Zheng, Zhao Yong, Zhang Dong, Qi Baiwen, Xiao Weidong, Hu Xiang, Yu Aixi
Department of Orthopaedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People's Republic of China,
Drug Des Devel Ther. 2019 Apr 5;13:1077-1086. doi: 10.2147/DDDT.S195937. eCollection 2019.
LLP2A-alendronate (LLP2A-Ale) is a novel bone-seeking compound that recruits mesenchymal stem cells to the bone surface and stimulates bone formation. The purpose of this study was to investigate the efficacy of LLP2A-Ale in the treatment of rabbit open fracture.
Thirty New Zealand White rabbits underwent radius mid-diaphyseal osteotomy and were randomly divided into control and treatment groups with fifteen rabbits in each group. The treatment group received only one injection of LLP2A-Ale (dosage 125 μg/kg), whereas the control group received one injection of PBS. X-ray images were taken to observe the course of fracture healing at 2, 4 and 6 weeks after treatment. Rabbits were sacrificed at 4 and 6 weeks post treatment. Calluses were then harvested and were subjected to histology, immunohistochemistry, molecular biology techniques and biomechanical test.
X-ray images showed that the LLP2A-Ale group exhibited abundant callus formation, stronger bony callus remodeling and earlier marrow cavity recanalization compared to the control group in a time-dependent manner. Histomorphological analysis revealed an advance in woven formation at 4 weeks and lamellar bone formation at 6 weeks in the LLP2A-Ale group. Moreover, gene and protein levels suggested that LLP2A-Ale promoted osteogenesis and angiogenesis probably via upregulating the expression of osteogenesis factors (including bone morphogenetic protein 2 and Runt-related transcription factor 2) and angiogenesis factors (vascular endothelial growth factor). Besides, the radius callus biomechanical properties were significantly enhanced in the LLP2A-Ale group compared with the control group at 6 weeks.
LLP2A-Ale can significantly promote open fracture healing in the rabbit model, probably through enhancing osteogenesis and angiogenesis.
LLP2A-阿仑膦酸盐（LLP2A-Ale）是一种新型的趋骨性化合物，可将间充质干细胞募集至骨表面并刺激骨形成。本研究旨在探讨LLP2A-Ale治疗兔开放性骨折的疗效。
30只新西兰白兔接受桡骨中段骨干截骨术，随机分为对照组和治疗组，每组15只。治疗组仅注射一次LLP2A-Ale（剂量125μg/kg），而对照组注射一次PBS。在治疗后2、4和6周拍摄X线片观察骨折愈合过程。治疗后4周和6周处死兔子。然后收集骨痂并进行组织学、免疫组织化学、分子生物学技术和生物力学测试。
X线片显示，与对照组相比，LLP2A-Ale组骨痂形成丰富，骨痂重塑更强，骨髓腔再通更早，且呈时间依赖性。组织形态学分析显示，LLP2A-Ale组在4周时编织骨形成提前，6周时板层骨形成提前。此外，基因和蛋白水平表明，LLP2A-Ale可能通过上调成骨因子（包括骨形态发生蛋白2和Runt相关转录因子2）和血管生成因子（血管内皮生长因子）的表达促进成骨和血管生成。此外，与对照组相比，LLP2A-Ale组在6周时桡骨骨痂的生物力学性能显著增强。
LLP2A-Ale可显著促进兔模型开放性骨折的愈合，可能是通过增强成骨和血管生成实现的。
