Establishment and assessment of small animal models of osteoarthritis

doi:10.3969/j.issn.2095-4344.2017.28.017

Abstract

Abstract:

BACKGROUND: Animal models of osteoarthritis are of great significance for the studies on its pathogenesis, prevention and treatment. There are various osteoarthritis models that certainly simulate the development of human osteoarthritis. Some stimulating factors have been found to participate in the occurrence and development of osteoarthritis.
OBJECTIVE: To review the recent researches about animal models of osteoarthritis at home and abroad, and to assess different modeling methods and some stimulating factors related to the occurrence and development of osteoarthritis.
METHODS: A computer-based retrieval of CNKI and PubMed databases before December 2016 was performed with the keywords of “osteoarthritis, animal models, stimulating factors, assessment grading system, outcome measurement” in Chinese and English, respectively. Finally 57 eligible papers were included for analysis.
RESULTS AND CONCLUSION: (1) In recent years, the osteoarthritis models are mainly established by doing damage to the cruciate ligaments and meniscus, and evaluated by Mankin score; the age of experimental animals tend to be younger. (2) Animals developed maturely are rational, so as to avoid the effect of self-healing caused by growth factors on osteoarthritis occurrence.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Models, Animal, Osteoarthritis, Tissue Engineering

CLC Number:

R318

Wu Wei, Li Hui, Zou Jun, Wang Miao. Establishment and assessment of small animal models of osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(28): 4529-4535.

Figures/Tables 4

2.2 刺激模型的因子骨关节炎的刺激因子加速了关节炎的发展，使之趋于恶化。骨关节炎是一种以软骨破坏、软骨下骨硬化及滑膜炎症为特征的退行性关节疾病，当软骨破损时由于软骨内无血管且缺乏神经支配，导致自愈能力差且软骨损伤初期对损伤疼痛敏感较低[26-27]。某些刺激因子通过对软骨的刺激持续破坏软骨，促进了骨关节炎的发展。刺激因子还可通过刺激滑膜大量分泌滑液，造成滑膜炎症，损害软骨，同样促进骨关节炎的发展[28]。本文将近几年常见刺激因子总结如下：刘杰等[13]将BLAB/C小鼠右膝进行6-8 ℃冷水刺激，1.5 h/d，未对小鼠右膝进行其他任何处理造成损伤，30 d后出现软骨损伤及滑膜炎症的症状。冷刺激可造成关节软骨损伤及滑膜炎症，促进骨关节炎的发展。Kim等[22]将C57BL/6大鼠内侧半月板切断制造模型后，分成自由活动组和限制活动组(仅限原地活动)，见图1。经过8周观察发现，额外规律运动(自由活动)可加重、加速骨关节炎的发展。在此基础上，每天对限制活动组大鼠进行跑步训练，依次分为400 m/d、800 m/d和1 200 m/d，再经过8周后发现，800 m/d的跑量对大鼠骨关节炎的程度加重最严重。骨关节炎发生时，额外的运动可促进其发展。钟名金等[29]研究发现，大白兔骨关节炎时，与笼养自由活动相比，早期合理的运动并不会加重膝关节软骨损伤(运动始于术后第5天，运动强度为5 d/周，10 min/d，跑台速度为0.3英里/h)。Wang等[25]研究中发现，仅单纯行上坡疲劳性跑步训练8周后(坡度+15°，跑台的训练频率为28 m/min、60 min/d、6 d/周)，软骨Ⅱ型胶原即可出现异常代谢。Tang等[30]研究发现，16-18周龄健康Wistar大鼠(未经任何处理)6周完成坡度5°的30 km跑台训练后，其软骨表面染色(India ink)变得不规律，异染性(safranin-O)几乎消失，Mankin评分达到骨关节炎水平。李炳辉等[31]将大白兔右膝用手术方法将其关节稳定性破坏后，再进行2 h/d的直立负重，并且制造经典的Hulth模型作比较。研究发现，直立负重可使关节软骨在短期内发生退变，促进骨关节炎的发展。流行病学研究中，骨关节炎与年龄密切相关。大数据研究发现，欧洲国家男性50岁、女性40岁以后骨关节炎的发生率明显上升，65岁以后为50%，75岁以后高达85%[32]。国内研究中发现，40岁以后患膝骨关节炎的概率增加，且随着年龄的增长，膝骨关节炎的发生呈不断增高的趋势，女性较男性患膝骨关节炎更高[33]。关节炎是老年人常见的退行性疾病，随着年龄的增长，关节软骨退变、破损，软骨下骨骨赘，滑膜炎症等日趋严重，影响膝关节的结构和功能。而女性绝经后，患骨关节炎的概率较高，其原因可能是雌激素水平下降后，通过作用于软骨和软骨下骨的雌激素受体，影响关节软骨周围内环境，导致软骨退变[34]。在周君等[35]研究中，成功利用去卵巢新西兰白兔，10周后其软骨出现明显退变。此过程中，没有进行任何造成膝关节损伤的措施。当运动强度过大可导致正常关节软骨损伤，且会加重已损伤的关节软骨及滑膜炎症等。负重及冷应激可刺激软骨、滑膜等，促进骨关节炎发展。年龄和女性绝经的因素也是影响骨关节炎发生发展的重要因子。此外，气压及湿度变化等因子也可以促进骨关节炎的发展[36-37]。详见表3。"

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