Expression of Sclerostin scFv and the Effect of Sclerostin scFv on Healing of Osteoporotic Femur Fracture in Rats

被引：13
作者：
Yao, Qi [1 ]
Ni, Jie [1 ]
Hou, Yu [1 ]
Ding, Lixiang [1 ]
Zhang, Licheng [2 ]
Jiang, Hua [3 ]
机构：
[1] Capital Med Univ, Beijing Shijitan Hosp, Dept Orthopaed, Beijing 100038, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed, Beijing 100853, Peoples R China
[3] Chinese Peoples Liberat Army Gen Hosp, Dept Stomatol, Beijing 100853, Peoples R China
来源：
CELL BIOCHEMISTRY AND BIOPHYSICS | 2014年 / 69卷 / 02期
基金：
中国国家自然科学基金;
关键词：
Osteoporosis; Bone healing; SOST; SOST-scFv; scFv; Sclerostin; Femur fracture; VH and VL gene; BONE-FORMATION; POTENTIAL TREATMENT; ANTIBODY; FUTURE; MASS;
D O I：
10.1007/s12013-013-9787-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：229 / 235
页数：7
相关论文
共 20 条
[1]   Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats [J].
Agholme, Fredrik ;
Li, Xiaodong ;
Isaksson, Hanna ;
Ke, Hua Zhu ;
Aspenberg, Per .
JOURNAL OF BONE AND MINERAL RESEARCH, 2010, 25 (11) :2412-2418
[2]   scFv Antibody: Principles and Clinical Application [J].
Ahmad, Zuhaida Asra ;
Yeap, Swee Keong ;
Ali, Abdul Manaf ;
Ho, Wan Yong ;
Alitheen, Noorjahan Banu Mohamed ;
Hamid, Muhajir .
CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2012,
[3]   Anabolic therapies [J].
Lane N.E. ;
Silverman S.L. .
Current Osteoporosis Reports, 2010, 8 (1) :23-27
[4]  
Lewiecki EM, 2011, DISCOV MED, V12, P263
[5]   Sclerostin monoclonal antibody therapy with AMG 785: a potential treatment for osteoporosis [J].
Lewiecki, E. Michael .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2011, 11 (01) :117-127
[6]   Inhibition of Sclerostin by Monoclonal Antibody Increases Bone Formation, Bone Mass, and Bone Strength in Aged Male Rats [J].
Li, Xiaodong ;
Warmington, Kelly S. ;
Niu, Qing-Tian ;
Asuncion, Franklin J. ;
Barrero, Mauricio ;
Grisanti, Mario ;
Dwyer, Denise ;
Stouch, Brian ;
Thway, Theingi M. ;
Stolina, Marina ;
Ominsky, Michael S. ;
Kostenuik, Paul J. ;
Simonet, William S. ;
Paszty, Chris ;
Ke, Hua Zhu .
JOURNAL OF BONE AND MINERAL RESEARCH, 2010, 25 (12) :2371-2380
[7]  
Luo Dong, 1995, Journal of Biochemistry (Tokyo), V118, P825
[8]   PHAGE ANTIBODIES - FILAMENTOUS PHAGE DISPLAYING ANTIBODY VARIABLE DOMAINS [J].
MCCAFFERTY, J ;
GRIFFITHS, AD ;
WINTER, G ;
CHISWELL, DJ .
NATURE, 1990, 348 (6301) :552-554
[9]   Sclerostin: Current Knowledge and Future Perspectives [J].
Moester, M. J. C. ;
Papapoulos, S. E. ;
Lowik, C. W. G. M. ;
van Bezooijen, R. L. .
CALCIFIED TISSUE INTERNATIONAL, 2010, 87 (02) :99-107
[10]   Inhibition of Sclerostin by Monoclonal Antibody Enhances Bone Healing and Improves Bone Density and Strength of Nonfractured Bones [J].
Ominsky, Michael S. ;
Li, Chaoyang ;
Li, Xiaodong ;
Tan, Hong L. ;
Lee, Edward ;
Barrero, Mauricio ;
Asuncion, Franklin J. ;
Dwyer, Denise ;
Han, Chun-Ya ;
Vlasseros, Fay ;
Samadfam, Rana ;
Jolette, Jacquelin ;
Smith, Susan Y. ;
Stolina, Marina ;
Lacey, David L. ;
Simonet, William S. ;
Paszty, Chris ;
Li, Gang ;
Ke, Hua Z. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2011, 26 (05) :1012-1021
12