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硬化蛋白单克隆抗体在大鼠开放性截骨模型中增强了骨折愈合。

Sclerostin monoclonal antibody enhanced bone fracture healing in an open osteotomy model in rats.

作者信息

Suen Pui Kit, He Yi-Xin, Chow Dick Ho Kiu, Huang Le, Li Chaoyang, Ke Hua Zhu, Ominsky Michael S, Qin Ling

机构信息

Department of Orthopaedics and Traumatology, Lui Che Woo Institute of Innovation Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.

出版信息

J Orthop Res. 2014 Aug;32(8):997-1005. doi: 10.1002/jor.22636. Epub 2014 Apr 30.

Abstract

Sclerostin is a negative regulator of bone formation. Sclerostin monoclonal antibody (Scl-Ab) treatment promoted bone healing in various animal models. To further evaluate the healing efficiency of Scl-Ab in osteotomy healing, we investigated the time course effects of systemic administration of Scl-Ab on fracture repair in rat femoral osteotomy model. A total of 120 six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were treated with vehicle or Scl-Ab treatment for 3, 6, or 9 weeks. Fracture healing was evaluated by radiography, micro-CT, micro-CT based angiography, 4-point bending mechanical test and histological assessment. Scl-Ab treatment resulted in significantly higher total mineralized callus volume fraction, BMD and enhanced neovascularization. Histologically, Scl-Ab treatment resulted in a significant reduction in fracture callus cartilage at week 6 and increase in bone volume at week 9, associated with a greater proportion of newly formed bone area at week 6 and 9 by fluorescence microscopy. Mechanical testing showed significantly higher ultimate load in Scl-Ab treatment group at week 6 and 9. This study has demonstrated that Scl-Ab treatment enhanced bone healing in a rat femoral osteotomy model, as reflected in increased bone formation, bone mass and bone strength.

摘要

硬化素是骨形成的负调节因子。硬化素单克隆抗体(Scl-Ab)治疗可促进多种动物模型的骨愈合。为进一步评估Scl-Ab在截骨愈合中的愈合效率,我们研究了在大鼠股骨截骨模型中全身给予Scl-Ab对骨折修复的时间进程影响。总共120只6个月大的雄性SD大鼠在右股骨中轴进行横向截骨。大鼠接受载体或Scl-Ab治疗3、6或9周。通过X线摄影、显微CT、基于显微CT的血管造影、4点弯曲力学试验和组织学评估来评价骨折愈合情况。Scl-Ab治疗导致矿化骨痂总体积分数、骨密度显著升高,新生血管形成增加。组织学上,Scl-Ab治疗在第6周时导致骨折痂软骨显著减少,在第9周时骨体积增加,通过荧光显微镜观察,在第6周和第9周时新形成骨面积的比例更大。力学测试显示,在第6周和第9周时,Scl-Ab治疗组的极限载荷显著更高。本研究表明,Scl-Ab治疗可增强大鼠股骨截骨模型中的骨愈合,表现为骨形成、骨量和骨强度增加。

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