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骨硬化蛋白 scFv 的表达及其对骨质疏松性股骨骨折愈合的影响。

Expression of sclerostin scFv and the effect of sclerostin scFv on healing of osteoporotic femur fracture in rats.

机构信息

Department of Orthopaedics, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing, 100038, China.

出版信息

Cell Biochem Biophys. 2014 Jun;69(2):229-35. doi: 10.1007/s12013-013-9787-1.

Abstract

Osteoporosis is a systemic metabolic disease characterized by low bone mass with deterioration of the bony microstructure which leads to both bone brittleness and increased risk of fracture. Sclerostin is a protein encoded by the SOST gene which is specifically expressed in osteocyte. Monoclonal antibodies of sclerostin can promote bone formation by antagonizing its inhibitory action. However, the effectiveness of monoclonal antibodies to exert such effects are limited by the large molecular mass and high immunogenicity. Here, we report that we purified a high immune affinity, single-chain antibody of SOST: SOST-single-chain Fv (scFv). Real-time polymerase chain reaction amplification of the variable regions of the heavy- and light-chain gene from a secretory anti-SOST antibody was performed. Animal experiments showed that SOST-scFv promoted bone healing in a rat model of osteoporosis.

摘要

骨质疏松症是一种以低骨量和骨微观结构恶化为特征的全身性代谢性疾病,导致骨脆性增加和骨折风险增加。骨硬化蛋白是 SOST 基因编码的一种蛋白质,特异性表达于骨细胞。骨硬化蛋白的单克隆抗体可通过拮抗其抑制作用促进骨形成。然而,单克隆抗体发挥这种作用的有效性受到其较大的分子量和高免疫原性的限制。在这里,我们报告我们纯化了一种具有高免疫亲和力的 SOST 单链抗体:SOST-单链 Fv(scFv)。从分泌抗 SOST 抗体的重链和轻链基因的可变区进行实时聚合酶链反应扩增。动物实验表明,SOST-scFv 可促进骨质疏松大鼠模型的骨愈合。

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