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

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

Daniel F McWilliams  1   2 , Mohsen Shahtaheri  1   2 , Soraya Koushesh  3 , Chitra Joseph  1   2 , Peter Rw Gowler  4 , Luting Xu  4 , Victoria Chapman  4 , Nidhi Sofat  3 , David A Walsh  1   2   5
Affiliations

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

Daniel F McWilliams et al. Osteoarthr Cartil Open. .

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.

Keywords: Bone marrow lesions; Histology; Meniscectomy; Monoiodoacetate; Osteoarthritis; Rat.

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Conflict of interest statement

DAW has grant support from 10.13039/100004312Eli Lilly & Company, 10.13039/100009032Pfizer Ltd, GSK Ltd, 10.13039/501100024580Orion Pharma, 10.13039/100011110UCB. DAW - Consultancy fees paid to University of Nottingham; Contura International A/S, Glaxo SmithKline, AKL Research and Development Ltd, Pfizer Ltd, Abbvie Ltd, Ely Lilly & Co.Ltd, Galapagos Ltd., Reckitt Benckiser Health Ltd. DAW - Speaker fees paid to University of Nottingham; Medscape International, Pfizer Ltd. DFM has grant support from 10.13039/100004312Eli Lilly & Company, 10.13039/100009032Pfizer Ltd. NS has grant support from 10.13039/100008021Bristol Myers Squibb, 10.13039/100004312Eli Lilly & Company and 10.13039/100009032Pfizer Ltd.

Figures

Fig. 1
Fig. 1
Features of the OABS in rat medial tibial plateau. A: Cyst (indicated by arrow). B: Vessels (arrows indicate vessels within the subchondral region). C: Vessels invading the cartilage (vessel within the cartilage indicated by arrow), D: Cartilage island (indicated by arrow). E: Thickened trabeculae (trabeculae indicated by arrows). F: Inflammation (examples of inflammatory cell infiltrates indicated by arrows). G: Fibrosis (example indicated by arrow). H: Normal appearance of subchondral region (at low power), with no cysts, no regions of inflammation, no regions of fibrosis, no cartilage invasion, no cartilage islands. ∗ ​= ​articular cartilage, ˆ ​= ​subchondral region.scale bars ​= ​100 ​μm.
Fig. 2
Fig. 2
Box and whiskers plot of rOABS median, IQR and range, with each datapoint included and jittered. Key, mia ​= ​monoiodoacetate, mnx ​= ​meniscal transection, sham ​= ​sham surgery, veh ​= ​vehicle.
Fig. 3
Fig. 3
A: rOABS vs weight bearing asymmetry (percentage) and B: paw withdraw threshold (g). Points are jittered to prevent overlapping.
See this image and copyright information in PMC

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