Sclerostin Monoclonal Antibody Enhanced Bone Fracture Healing in an Open Osteotomy Model in Rats

被引：87

作者：

Suen, Pui Kit ^{[1
]}

He, Yi-Xin ^{[1
]}

Chow, Dick Ho Kiu ^{[1
]}

Huang, Le ^{[1
]}

Li, Chaoyang ^{[2
]}

Ke, Hua Zhu ^{[2
]}

Ominsky, Michael S. ^{[2
]}

Qin, Ling ^{[1
,3
]}

机构：

[1] Chinese Univ Hong Kong, Fac Med, Lui Che Woo Inst Innovat Med, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China

[2] Amgen Inc, Metab Disorders Res, Thousand Oaks, CA 91320 USA

[3] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China

来源：

JOURNAL OF ORTHOPAEDIC RESEARCH | 2014年 / 32卷 / 08期

关键词：

sclerostin; sclerostin monoclonal antibody; osteotomy; fracture healing; TRANSCRIPTION FACTOR OSTERIX; GROWTH-FACTOR VEGF; DISTRACTION OSTEOGENESIS; STRENGTH; ANGIOGENESIS; DEFECT; REGENERATION; INHIBITION; EXPRESSION; DELETION;

D O I：

10.1002/jor.22636

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

100224 [整形外科学];

摘要：

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. (C) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

引用

页码：997 / 1005

页数：9

共 40 条

[1]

Agholme F, 2011, ACTA ORTHOP, V82, P125, DOI [10.3109/17453674.2011.625539, 10.3109/17453674.2011.572252]

[2]

Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST) [J].

Balemans, W ;

Ebeling, M ;

Patel, N ;

Van Hul, E ;

Olson, P ;

Dioszegi, M ;

Lacza, C ;

Wuyts, W ;

Van den Ende, J ;

Willems, P ;

Paes-Alves, AF ;

Hill, S ;

Bueno, M ;

Ramos, FJ ;

Tacconi, P ;

Dikkers, FG ;

Stratakis, C ;

Lindpaintner, K ;

Vickery, B ;

Foernzler, D ;

Van Hul, W .

HUMAN MOLECULAR GENETICS, 2001, 10 (05) :537-543

[3]

Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength [J].

Bosemark, Per ;

Isaksson, Hanna ;

McDonald, Michelle M. ;

Little, David G. ;

Tagil, Magnus .

ACTA ORTHOPAEDICA, 2013, 84 (01) :106-111

[4]

HIF-1α Inhibits Wnt Signaling Pathway by Activating Sost Expression in Osteoblasts [J].

Chen, Dafu ;

Li, Yang ;

Zhou, Zhiyu ;

Wu, Chengai ;

Xing, Yonggang ;

Zou, Xuenong ;

Tian, Wei ;

Zhang, Chi .

PLOS ONE, 2013, 8 (06)

[5]

Synergistic Inhibition of Wnt Pathway by HIF-1α and Osteoblast-Specific Transcription Factor Osterix (Osx) in Osteoblasts [J].

Chen, Dafu ;

Li, Yang ;

Zhou, Zhiyu ;

Xing, Yonggang ;

Zhong, Yu ;

Zou, Xuenong ;

Tian, Wei ;

Zhang, Chi .

PLOS ONE, 2012, 7 (12)

[6]

Osteoblast-specific transcription factor Osterix (Osx) and HIF-1α cooperatively regulate gene expression of vascular endothelial growth factor (VEGF) [J].

Chen, Dafu ;

Tian, Wei ;

Li, Yang ;

Tang, Wanjin ;

Zhang, Chi .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 424 (01) :176-181

[7]

Extracorporeal Shockwave Therapy for Treatment of Delayed Tendon-Bone Insertion Healing in a Rabbit Model A Dose-Response Study [J].

Chow, Dick Ho Kiu ;

Suen, Pui Kit ;

Fu, Lai Hong ;

Cheung, Wing Hoi ;

Leung, Kwok Sui ;

Wong, Margaret Wan Nar ;

Qin, Ling .

AMERICAN JOURNAL OF SPORTS MEDICINE, 2012, 40 (12) :2862-2871

[8]

Colnot C, 2009, J BONE MINER RES, V24, P274, DOI [10.1359/jbmr.081003, 10.1359/JBMR.081003]

[9]

Easwaran V, 2003, CANCER RES, V63, P3145

[10]

Ellman R, 2012, J BONE MINER RES S1, V27

← 1 2 3 4 →