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Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model
He, Yi-Xin1; Zhang, Ge1; Pan, Xiao-Hua1,3; Liu, Zhong1; Zheng, Li-Zhen1; Chan, Chun-Wai1; Lee, Kwong-Man4; Cao, Yong-Ping5; Li, Gang1; Wei, Lei6,7; Hung, Leung-Kim1; Leung, Kwok-Sui1,2; Qin, Ling1,2
关键词Osteoporosis Drill-hole Micro-ct Mouse Bone Healing
刊名BONE
2011-06-01
DOI10.1016/j.bone.2011.03.720
48期:6页:1388-1400
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]ESTROGEN-RECEPTOR-BETA ; FRACTURE REPAIR ; INTERNAL-FIXATION ; MINERAL DENSITY ; DEFICIENT MICE ; STEM-CELLS ; EXPRESSION ; GROWTH ; RATS ; CALLUS
英文摘要

Objective: To establish a drill-hole defect model in osteoporotic mouse femur by comparing temporal cortical bone healing pattern between OVX-induced osteoporotic bone and sham-operated bone.

Methods: 3-month-old female C57BL/6 mice were randomly divided into an ovariectomy group (OVX) and a sham-operated group (Sham). At 6 weeks post-surgery, 7 mice from each group were sacrificed to examine the distal femur and femoral shaft by both micro-CT and mechanical testing for confirming established osteoporosis induced by OVX. In the remaining mice, a cortical bone defect 0.8 mm in diameter was created on the mid-diaphysis of the right femur. The local repair process at days 0, 3, 7, 10,14 and 21 after creation of the drill-hole was in vivo monitored by high-resolution micro-CT scanning. At each time point, each animal was scanned four times and was removed from the scanner between scans to determine reproducibility. Mice were sacrificed at each time point (n = 12 at days 0, 3, 7, 10 and 14; n = 20 at day 21). Before sacrifice, sera were collected to examine expression of bone formation marker P1NP (procollagen type 1 N-terminal propeptide) and bone resorption marker CTX (C-terminal telopeptide of type I collagen). After sacrifice, callus samples were collected and subjected to the following analyses: micro-CT-based angiography; histological examination; immunohistochemical staining to determine estrogen receptor expression; quantitative real-time PCR analysis of collagen type I, collagen type II, collagen type X, osteocalcin, tartrate-resistant acid phosphatase, estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) gene expression; and three-point mechanical testing.

Results: At 6 weeks post-surgery, OVX mice had significantly lower bone mass, impaired bone micro architecture and compromised mechanical properties compared to the Sham mice. In vivo micro-CT analysis revealed that the bone volume fraction in the defect region was significantly lower in the OVX group from day 10 to day 21 post-injury as compared to the Sham group, and was significantly lower in the intra-medulla region in the OVX group from day 7 to day 14 as compared to the Sham group, consistent with the histological data. Analysis of bone biochemical markers indicated that circulating P1NP levels normalized by baseline in the OVX mice were significantly lower than in the Sham mice from day 7 to day 10, and that temporal expression of circulating CTX levels normalized by baseline was also lower in the OVX mice as compared to the Sham mice. These results were consistent with quantitative real-time PCR analysis. ER alpha mRNA expression was significantly lower in the OVX mice, whereas ER beta mRNA expression was significantly higher in the OVX mice as compared to the Sham mice at all time points examined, consistent with immunohistochemical staining. The restoration of femoral mechanical property, determined based on ultimate load and energy-to-failure, was significantly lower in the OVX mice than in the Sham mice. In addition, in vivo micro-CT scanning for quantifying new bone formation in the defect site was highly reproducible in this model.

Conclusion: The bone healing of the drill-hole defect was impaired in mice with OVX-induced osteoporosis. The present study provides a model to investigate the functional role of specific gene in osteoporotic bone healing and may facilitate development of novel therapeutic strategies for promoting osteoporotic bone healing. (C) 2011 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000290974200022
项目编号S-08-74Z ; 2008.1.063
资助机构AO Research Grant ; CUHK
引用统计
被引频次:84[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52567
专题北京大学第一临床医学院_骨科
作者单位1.Chinese Univ Hong Kong, Dept Orthopaed & Traumatol, Musculoskeletal Res Lab, Shatin, Hong Kong, Peoples R China
2.Chinese Acad Sci, Shenzhen Inst Adv Technol, Inst Biomed & Hlth Engn, Translat Med Res & Dev Ctr, Shenzhen 518055, Peoples R China
3.Ji Nan Univ, Shenzhen Peoples Hosp, Hosp Med Coll 2, Dept Orthoped, Shenzhen 518020, Peoples R China
4.Chinese Univ Hong Kong, Lee Hysan Clin Res Lab, Shatin, Hong Kong, Peoples R China
5.Peking Univ, Hosp 1, Dept Orthoped, Beijing 100034, Peoples R China
6.Brown Univ, Warren Alpert Med Sch, Dept Orthopaed, Providence, RI 02912 USA
7.Shanxi Med Univ, Hosp 2, Dept Orthopaed, Shanxi Key Lab Bone & Soft Tissue Injury Repair, Taiyuan 030001, Peoples R China
推荐引用方式
GB/T 7714
He, Yi-Xin,Zhang, Ge,Pan, Xiao-Hua,et al. Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model[J]. BONE,2011,48(6):1388-1400.
APA He, Yi-Xin.,Zhang, Ge.,Pan, Xiao-Hua.,Liu, Zhong.,Zheng, Li-Zhen.,...&Qin, Ling.(2011).Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model.BONE,48(6),1388-1400.
MLA He, Yi-Xin,et al."Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model".BONE 48.6(2011):1388-1400.
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