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与人类骨髓损伤和疼痛相关的组织病理学大鼠骨关节炎骨评分。

The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain.

作者信息

McWilliams Daniel F, Shahtaheri Mohsen, Koushesh Soraya, Joseph Chitra, Gowler Peter Rw, Xu Luting, Chapman Victoria, Sofat Nidhi, Walsh David A

机构信息

Pain Centre Versus Arthritis and Academic Unit of Injury, Recovery and Inflammation Sciences, University of Nottingham, UK.

NIHR Biomedical Research Centre, Nottingham University Hospitals, UK.

出版信息

Osteoarthr Cartil Open. 2024 Nov 27;7(1):100544. doi: 10.1016/j.ocarto.2024.100544. eCollection 2025 Mar.

DOI:10.1016/j.ocarto.2024.100544
PMID:39717525
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11665527/
Abstract

OBJECTIVES

Histological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.

METHODS

Rats (n ​= ​8-10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery. Pain behaviour (weight bearing asymmetry and mechanical hindpaw withdrawal thresholds (PWTs)) were measured and knee samples obtained. Features associated with BMLs were evaluated using haematoxylin and eosin or Safranin-O stained knee sections. Sections were scored for chondropathy, osteophytes, synovitis and with the human OA Bone Score modified for rats (rOABS). rOABS reliability was assessed with intraclass correlation coefficient (ICC), groups were compared using Mann-Whitney U-tests, and associations examined with Spearman's rho.

RESULTS

OABS features were more prevalent in each OA pain group than in controls. rOABS displayed good inter-rater reliability (ICC ​= ​0.79). rOABS was higher in each model than controls; MIA 3.0 (2.3-4.0) vs vehicle 0.0 (0.0-0.0), and MNX 4.0 (2.3-4.8) vs sham 0.0 (0.0-0.0), each p ​< ​0.003. rOABS was associated with OA cartilage involvement (rho ​= ​0.69, p ​< ​0.001), osteophyte (rho ​= ​0.61, p ​< ​0.001) and synovial inflammation (rho ​= ​0.76, p ​< ​0.001). Higher rOABS was associated with pain behaviour: weight bearing asymmetry (rho ​= ​0.65, p ​< ​0.001) and PWT (rho ​= ​-0.47, p ​= ​0.003).

CONCLUSIONS

Subchondral pathology in rat OA models resembles human subchondral BMLs. rOABS reliably measured subchondral pathology and was associated with OA structure and pain behaviour.

摘要

目的

炎症、纤维化、血管形成、软骨岛、进入软骨的血管、增厚的小梁和囊肿等组织学骨软骨特征与人类膝关节骨关节炎(OA)中的骨髓损伤(BMLs)相关。我们识别并开发了一种方法,用于对两种大鼠OA膝关节疼痛模型中的可比病理学进行评分。

方法

将大鼠(每组n = 8 - 10只)注射单碘乙酸盐(MIA)或生理盐水,或进行半月板横断术(MNX)或假手术。测量疼痛行为(负重不对称和机械性后爪撤离阈值(PWTs))并获取膝关节样本。使用苏木精和伊红或番红O染色的膝关节切片评估与BMLs相关的特征。对切片进行软骨病、骨赘、滑膜炎评分,并使用针对大鼠修改后的人类OA骨评分(rOABS)进行评分。使用组内相关系数(ICC)评估rOABS的可靠性,使用Mann-Whitney U检验比较各组,并使用Spearman秩相关系数检验相关性。

结果

每个OA疼痛组中的OABS特征比对照组更普遍。rOABS显示出良好的评分者间可靠性(ICC = 0.79)。每个模型中的rOABS均高于对照组;MIA组为3.0(2.3 - 4.0),而赋形剂组为0.0(0.0 - 0.0),MNX组为4.0(2.3 - 4.8),假手术组为0.0(0.0 - 0.0),每组p < 0.003。rOABS与OA软骨受累相关(rho = 0.69,p < 0.001)、骨赘(rho = 0.61,p < 0.001)和滑膜炎(rho = 0.76,p < 0.001)。较高的rOABS与疼痛行为相关:负重不对称(rho = 0.65,p < 0.001)和PWT(rho = -0.47,p = 0.003)。

结论

大鼠OA模型中的软骨下病理与人类软骨下BMLs相似。rOABS可靠地测量了软骨下病理,并与OA结构和疼痛行为相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc98/11665527/4be0f02ad4c9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc98/11665527/5c784d61248d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc98/11665527/7ce5ab99d662/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc98/11665527/4be0f02ad4c9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc98/11665527/5c784d61248d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc98/11665527/7ce5ab99d662/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc98/11665527/4be0f02ad4c9/gr3.jpg

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