Inactivation of the gene encoding procalcitonin prevents antibody-mediated arthritis.

Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2023 May

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Procalcitonin (PCT) is applied as a sensitive biomarker to exclude bacterial infections in patients with rheumatoid arthritis (RA) flare-ups. Beyond its diagnostic value, little is known about the pathophysiological role of PCT in RA. Collagen antibody-induced arthritis (CAIA) was induced in Calca-deficient mice (Calca-/-), lacking PCT (n = 15), and wild-type (WT) mice (n = 13), while control (CTRL) animals (n = 8 for each genotype) received phosphate-buffered saline. Arthritis severity and grip strength were assessed daily for 10 or 48 days. Articular inflammation, cartilage degradation, and bone lesions were assessed by histology, gene expression analysis, and µ-computed tomography. Serum PCT levels and intra-articular PCT expression increased following CAIA induction. While WT animals developed a full arthritic phenotype, Calca-deficient mice were protected from clinical and histological signs of arthritis and grip strength was preserved. Cartilage turnover markers and Tnfa were exclusively elevated in WT mice. Calca-deficient animals expressed increased levels of Il1b. Decreased bone surface and increased subchondral bone porosity were observed in WT mice, while Calca-deficiency preserved bone integrity. The inactivation of Calca and thereby PCT provided full protection from joint inflammation and arthritic bone loss in mice exposed to CAIA. Together with our previous findings on the pathophysiological function of Calca-derived peptides, these data indicate an independent pro-inflammatory role of PCT in RA. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Citation

Tazio Maleitzke, Tamara Dietrich, Alexander Hildebrandt, Jérôme Weber, Jessika Appelt, Denise Jahn, Ellen Otto, Dario Zocholl, Shan Jiang, Anke Baranowsky, Georg N Duda, Serafeim Tsitsilonis, Johannes Keller. Inactivation of the gene encoding procalcitonin prevents antibody-mediated arthritis. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2023 May;72(5):1069-1081