Assessing the Effects of Parthenolide on Inflammation, Bone Loss, and Glial Cells within a Collagen Antibody-Induced Arthritis Mouse Model

B. Williams, F. Lees, H. Tsangari, M. R. Hutchinson, E. Perilli, T. N. Crotti

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Rheumatoid arthritis is characterised by a chronic inflammatory response resulting in destruction of the joint and significant pain. Although a range of treatments are available to control disease activity in RA, bone destruction and joint pain exist despite suppression of inflammation. This study is aimed at assessing the effects of parthenolide (PAR) on paw inflammation, bone destruction, and pain-like behaviour in a mild collagen antibody-induced arthritis (CAIA) mouse model. CAIA was induced in BALB/c mice and treated daily with 1 mg/kg or 4 mg/kg PAR. Clinical paw inflammation was scored daily, and mechanical hypersensitivity was assessed on alternate days. At end point, bone volume and swelling in the paws were assessed using micro-CT. Paw tissue sections were assessed for inflammation and pre-/osteoclast-like cells. The lumbar spinal cord and the periaqueductal grey (PAG) and rostral ventromedulla (RVM) regions of the brain were stained for glial fibrillary acidic protein (GFAP) and ionised calcium-binding adaptor molecule 1 (IBA1) to assess for glial reactivity. Paw scores increased in CAIA mice from days 5-10 and were reduced with 1 mg/kg and 4 mg/kg PAR on days 8-10. Osteoclast-like cells on the bone surface of the radiocarpal joint and within the soft tissue of the hind paw were significantly lower following PAR treatment (p<0.005). GFAP- A nd IBA1-positive cells in the PAG and RVM were significantly lower following treatment with 1 mg/kg (p<0.0001 and p=0.0004, respectively) and 4 mg/kg PAR (p<0.0001 and p=0.001, respectively). In the lumbar spinal cord, IBA1-positive cells were significantly lower in CAIA mice treated with 4 mg/kg PAR (p=0.001). The findings indicate a suppressive effect of both low- A nd moderate-dose PAR on paw inflammation, osteoclast presence, and glial cell reactivity in a mild CAIA mouse model.

    Original languageEnglish
    Article number6245798
    Number of pages13
    JournalMediators of Inflammation
    Volume2020
    DOIs
    Publication statusPublished - 4 Mar 2020

    Bibliographical note

    Copyright © 2020 B. Williams et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Keywords

    • Rheumatoid arthritis
    • inflammation
    • Parthenolide
    • Pain

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