Recommendations For a Standardized Approach to Histopathologic Evaluation of Synovial Membrane in Murine Models of Experimental Osteoarthritis.

Autor: Obeidat AM; Division of Rheumatology, Department of Internal Medicine, Rush University Medical College, Chicago IL., Kim SY; University of Pennsylvania School of Engineering and Applied Sciences, Philadelphia PA 19104., Burt KG; Translational Musculoskeletal Research Center, Corp. Michael J Crescenz VA Medical Center, Philadelphia PA 19104.; Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104., Hu B; Translational Musculoskeletal Research Center, Corp. Michael J Crescenz VA Medical Center, Philadelphia PA 19104.; Division of Rheumatology, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104., Li J; Division of Rheumatology, Department of Internal Medicine, Rush University Medical College, Chicago IL., Ishihara S; Division of Rheumatology, Department of Internal Medicine, Rush University Medical College, Chicago IL., Xiao R; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.; Department of Pediatrics Division of Biostatistics, Children's Hospital of Philadelphia, Philadelphia, PA 19104., Miller RE; Division of Rheumatology, Department of Internal Medicine, Rush University Medical College, Chicago IL., Little C; Kolling Institute, Faculty of Medicine and Health, The University of Sydney, NSW, 2065, Australia., Malfait AM; Division of Rheumatology, Department of Internal Medicine, Rush University Medical College, Chicago IL., Scanzello CR; Translational Musculoskeletal Research Center, Corp. Michael J Crescenz VA Medical Center, Philadelphia PA 19104.; Division of Rheumatology, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 18. Date of Electronic Publication: 2023 Oct 18.
DOI: 10.1101/2023.10.14.562259
Abstrakt: Background: Synovial pathology has been linked to osteoarthritis (OA) pain in patients. Microscopic grading systems for synovial changes in human OA have been described, but a standardized approach for murine models of OA is needed. We sought to develop a reproducible approach and set of minimum recommendations for synovial histopathology in mouse models of OA.
Methods: Coronal and sagittal sections from male mouse knee joints subjected to destabilization of medial meniscus (DMM) or partial meniscectomy (PMX) were collected as part of other studies. Stains included Hematoxylin and Eosin (H&E), Toluidine Blue (T-Blue) and Safranin O/Fast Green (Saf-O). Four blinded readers graded pathological features (hyperplasia, cellularity, and fibrosis) at specific anatomic locations in the medial and lateral compartments. Inter-reader reliability of each feature was determined.
Results: There was acceptable to very good agreement between raters. After DMM, increased hyperplasia and cellularity and a trend towards increased fibrosis were observed 6 weeks after DMM in the medial locations, and persisted up to 16 weeks. In the PMX model, cellularity and hyperplasia were evident in both medial and lateral compartments while fibrotic changes were largely seen on the medial side. Synovial changes were consistent from section to section in the mid-joint area mice. H&E, T-blue, and Saf-O stains resulted in comparable reliability.
Conclusions: To allow for a standard evaluation that can be implemented and compared across labs and studies, we recommend using 3 readers to evaluate a minimum set of 3 pathological features at standardized anatomic areas. Pre-defining areas to be scored, and reliability for each pathologic feature should be considered.
Competing Interests: Competing interests: The following authors declare no conflicts of interest: AMO, SYK, KGB, BH, SI, JL, RX. REM serves as an Associate Editor of Arthritis & Rheumatology. CBL serves as Deputy Editor for Osteoarthritis & Cartilage, received consulting fees from Fidia Farmaceutici and Rotapharm, and conducts contract research for various pharmaceutical companies. AMM received consulting fees from Asahi Kasei Pharma Corporation, Orion, and 23andMe, and serves as the co-Editor-in-Chief of Osteoarthritis and Cartilage. CRS and REM serve as Associate Editors for Arthritis & Rheumatology, and are on the Editorial Board of Osteoarthritis & Cartilage. In addition, CRS is named as inventor on provisional patent applications regarding a novel method of treatment for osteoarthritis.
Databáze: MEDLINE