‘SMASH’ recommendations for standardised microscopic arthritis scoring of histological sections from inflammatory arthritis animal models

Abstract

Animal models for inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic arthritis are widely accepted and frequently used to identify pathological mechanisms and validate novel therapeutic strategies. Unfortunately, many publications reporting on these animal studies lack detailed description and appropriate assessment of the distinct histopathological features of arthritis: joint inflammation, cartilage damage and bone erosion. Therefore, the European consortium BeTheCure, consisting of 38 academic and industrial partners from 15 countries, set as goal to standardise the histological evaluation of joint sections from animal models of inflammatory arthritis. The consensual approach of a task force including 16 academic and industrial scientists as well as laboratory technicians has resulted in the development of the Standardised Microscopic Arthritis Scoring of Histological sections (‘SMASH’) recommendations for a standardised processing and microscopic scoring of the characteristic histopathological features of arthritis, exemplified by four different rodent models for arthritis: murine collagen-induced arthritis, collagen–antibody-induced arthritis, human tumour necrosis factor transgenic Tg197 mice and rat pristane-induced arthritis, applicable to any other inflammatory arthritis model. Through standardisation, the SMASH recommendations are designed to improve and maximise the information derived from in vivo arthritis experiments and to promote reproducibility and transparent reporting on such studies. In this manuscript, we will discuss and provide recommendations for analysis of histological joint sections: identification of the regions of interest, sample preparation, staining procedures and quantitative scoring methods. In conclusion, awareness of the different features of the arthritis pathology in animal models of inflammatory arthritis is of utmost importance for reliable research outcome, and the standardised histological processing and scoring methods in these SMASH recommendations will help increase uniformity and reproducibility in preclinical research on inflammatory arthritis.

Greetings from the editor

“…Several points-to-consider or recommendations are presented in this June issue: one on the pathophysiology of COVID-19 (accompanied by an elegant editorial) 24 25 ; one on the important topic of adherence to treatment 26 ; and one on the standardisation of scoring in arthritis models, an area where standardisation had not been undertaken hitherto. 27 A review authored by one of the world's premier groups provides an important summary of current knowledge and prospects on functional genomics. 28 In the 'Heroes and Pillars of Rheumatology' section, eminent authors remind us of two major figures in rheumatology of the late 20th century into the most recent years, Charles L Christian and Joachim R Kalden, a US and a European hero, respectively, who have inspired the whole world with their research and personalities.…”

“…Several points-to-consider or recommendations are presented in this June issue: one on the pathophysiology of COVID-19 (accompanied by an elegant editorial) 24 25 ; one on the important topic of adherence to treatment 26 ; and one on the standardisation of scoring in arthritis models, an area where standardisation had not been undertaken hitherto. 27 A review authored by one of the world’s premier groups provides an important summary of current knowledge and prospects on functional genomics. 28 …”

Photodynamic Therapy Targeting Macrophages Using IRDye700DX-Liposomes Decreases Experimental Arthritis Development

“…To assess the joint inflammation, microscopically ankle joints were formalin-fixed, decalcified using formic acid and paraffin-embedded. The joints were subsequently cut into 7 µm sections, hematoxylin-and eosin-stained, and scored for the presence of inflammation according to the SMASH recommendations [23].…”

Inhibition of TGF-β Signaling Suppresses Th17 Differentiation and Promotes Treg Numbers but Does Not Reduce Experimental Arthritis.

“…Histology was processed and scored in line with the 'SMASH' recommendations for standardized microscopic arthritis scoring 21 . In short, isolated joints were xed for at least four days in 4% formaldehyde, decalci ed in 5% formic acid, and subsequently dehydrated and embedded in para n. Standard frontal sections of 7 µm were stained with H&E or Safranin O (SO) to study joint pathology.…”