The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat

The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat
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DOI:
10.1016/j.joca.2010.05.030
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发表时间:
2010-10-01
影响因子:
7
通讯作者:
Carlson, C. S.
Carlson, C. S.
中科院分区:
医学2区
文献类型:
--
作者:
Gerwin, N.;Bendele, A. M.;Carlson, C. S.

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目的 在缓解疾病骨关节炎 (OA) 药物的开发过程中,经常使用 OA 大鼠模型来首次评估体内疗效。然后,在进入人体试验之前,可以在更大的动物模型中测试大鼠模型中最有效的化合物。本研究的目的是描述用于大鼠不同 OA 模型的组织学评分系统,允许对不同研究人员获得的结果进行标准化和比较。方法在推荐这种大鼠组织学评分的通用范例时,考虑了作者对当前评分系统的经验以及在大鼠和人类 OA 研究中观察到的病变范围 考虑到新评分者的可重复性和易用性 可以采用额外的评分范例来进一步确定某些疾病缓解药物的具体效果 结果 虽然所描述的评分系统比推荐用于其他一些物种的修改后的 Mankin 评分更复杂,但可行性研究表明它很容易理解并且可以重复使用,即使是没有经验的评分者结论这里描述的评分范例有 已被发现对区分治疗具有足够的敏感性,并且具有高重现性 因此,我们建议将其用于评估不同的大鼠 OA 模型以及评估这些模型中治疗的疾病改善效果 (C) 2010 国际骨关节炎研究协会 由 Elsevier Ltd 出版 保留所有权利
Objective During the development of disease-modifying osteoarthritis (OA) drugs, rat models of OA are frequently used for a first assessment of in vivo efficacy. The most efficacious compound in the rat model may then be tested in a larger animal model before entering human trials The aim of this study was to describe a histologic scoring system for use in different models of OA in rats that allows standardization and comparison of results obtained by different investigatorsMethods The experience of the authors with current scoring systems and the range of lesions observed in rat and human OA studies were considered in recommending this common paradigm for rat histologic scoring Considerations were made for reproducibility and ease of use for new scorers Additional scoring paradigms may be employed to further Identify specific effects of some disease-modifying drugsResults Although the described scoring system is more complex than the modified Mankin scores, which are recommended for some other species, the tenability study showed that it is easily understood and can be reproducibly used, even by Inexperienced scorersConclusions The scoring paradigm described here has been found to be sufficiently sensitive to discriminate between treatments and to have high reproducibility Therefore we recommend its use for evaluation of different rat OA models as well as assessment of disease-modifying effects of treatments in these models (C) 2010 Osteoarthritis Research Society International Published by Elsevier Ltd All rights reserved