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

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

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 to 4.0) vs vehicle 0.0 (0.0 to 0.0), and MNX 4.0 (2.3 to 4.8) vs sham 0.0 (0.0 to 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.

Citation

McWilliams, D. F., Shahtaheri, M., Koushesh, S., Joseph, C., Gowler, P. R., Xu, L., Chapman, V., Sofat, N., & Walsh, D. A. (2025). The rat osteoarthritis bone score for histological pathology relevant to human bone marrow lesions and pain. Osteoarthritis and Cartilage Open, 7(1), Article 100544. https://doi.org/10.1016/j.ocarto.2024.100544

• Journal Article Type: Article
• Acceptance Date: Nov 14, 2024
• Online Publication Date: Nov 27, 2024
• Publication Date: 2025-03
• Deposit Date: Dec 4, 2024
• Publicly Available Date: Dec 19, 2024
• Journal: Osteoarthritis and Cartilage Open
• Print ISSN: 2665-9131
• Electronic ISSN: 2665-9131
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 1
• Article Number: 100544
• DOI: https://doi.org/10.1016/j.ocarto.2024.100544
• Public URL: https://nottingham-repository.worktribe.com/output/42594471
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2665913124001110