A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury

被引：91

作者：

Eltawil, N. M. ^{[1
]}

De Bari, C. ^{[2
]}

Achan, P. ^{[3
]}

Pitzalis, C. ^{[1
]}

Dell'Accio, F. ^{[1
]}

机构：

[1] Barts & London Queen Marys Sch Med & Dent, Ctr Expt Med & Rheumatol, William Harvey Res Inst, London, England

[2] Univ Aberdeen, Sch Med, Dept Med & Therapeut, Aberdeen AB9 2ZD, Scotland

[3] Barts & Royal London Hosp, London, England

来源：

OSTEOARTHRITIS AND CARTILAGE | 2009年 / 17卷 / 06期

基金：

英国医学研究理事会;

关键词：

Cartilage repair; Joint surface defects; Cartilage regeneration; Animal models; osteoarthritis; Cartilage injury; apoptosis; Metalloproteinases; regenerative medicine; FULL-THICKNESS DEFECTS; ARTICULAR-CARTILAGE; KNEE CARTILAGE; II COLLAGEN; OSTEOCHONDRAL DEFECTS; MECHANICAL INJURY; NATURAL-HISTORY; REPAIR; OSTEOARTHRITIS; ACTIVATION;

D O I：

10.1016/j.joca.2008.11.003

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：

Objectives: To generate and validate a murine model of joint surface repair following acute mechanical injury. Methods: Full thickness defects were generated in the patellar groove of C57BL/6 and DBA/1 mice by microsurgery. Control knees were either sham-operated or non-operated. Outcome was evaluated by histological scoring systems. Apoptosis and proliferation were studied using TUNEL and Phospho-Histone H3 staining, respectively. Type 11 collagen neo-deposition and degradation were evaluated by immunostaining using antibodies to the CPII telopeptide and C1,2C (Col2-3/4Cshort), respectively. Aggrecanases and matrix metalloproteinases (MMPs) activity were assessed by immunostaining for TEGE(373) and VDIPEN neo-epitopes. Results: Young 8-week-old DBA/1 mice displayed consistent and superior healing of the articular cartilage defect. Age-matched C57BL/6 mice repaired poorly and developed features of osteoarthritis (OA). Compared to C57BL/6, DBA/1 mice displayed a progressive decline of chondrocyte apoptosis, cell proliferation within the repair tissue, persistent type 11 collagen neo-deposition, less type 11 collagen degradation, less aggrecanases and more MMP-induced aggrecan degradation. Eight-month-old DBA/1 mice failed to repair, but, in contrast to age-matched C57BL/6 mice, developed no signs of OA. Conclusion: We have generated and validated a murine model of cartilage regeneration in which the outcome of joint surface injury is strain and age dependent. This model will allow, for the first time, the dissection of different pathways involved in joint surface regeneration in adult mammals using the powerful technology of mouse genetics. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

引用

页码：695 / 704

页数：10

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