The calcitonin receptor protects against bone loss and excessive inflammation in collagen antibody-induced arthritis

Tazio Maleitzke; Alexander Hildebrandt; Tamara Dietrich; Jessika Appelt; Denise Jahn; Ellen Otto; Dario Zocholl; Anke Baranowsky; Georg N Duda; Serafeim Tsitsilonis; Johannes Keller

doi:10.1016/j.isci.2021.103689

The calcitonin receptor protects against bone loss and excessive inflammation in collagen antibody-induced arthritis

iScience. 2021 Dec 24;25(1):103689. doi: 10.1016/j.isci.2021.103689. eCollection 2022 Jan 21.

Authors

Tazio Maleitzke^{1

2

3}, Alexander Hildebrandt^{1

2}, Tamara Dietrich^{1

2}, Jessika Appelt^{1

2}, Denise Jahn^{1

2}, Ellen Otto^{1

2}, Dario Zocholl⁴, Anke Baranowsky⁵, Georg N Duda², Serafeim Tsitsilonis^{1

2}, Johannes Keller^{3

5}

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany.
² Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany.
³ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, 10178 Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biometry and Clinical Epidemiology, 10117 Berlin, Germany.
⁵ Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany.

Abstract

Pharmacological application of teleost calcitonin (CT) has been shown to exert chondroprotective and anti-resorptive effects in patients with rheumatoid arthritis (RA). However, the role of endogenous CT that signals through the calcitonin receptor (CTR) remains elusive. Collagen II antibody-induced arthritis (CAIA) was stimulated in wild type (WT) and CTR-deficient (Calcr^-/-) mice. Animals were monitored over 10 or 48 days. Joint inflammation, cartilage degradation, and bone erosions were assessed by clinical arthritis score, histology, histomorphometry, gene expression analysis, and μ-computed tomography. CAIA was accompanied by elevated systemic CT levels and CTR expression in the articular cartilage. Inflammation, cartilage degradation, and systemic bone loss were more pronounced in Calcr^-/- CAIA mice. Expression of various pro-inflammatory, bone resorption, and catabolic cartilage markers were exclusively increased in Calcr^-/- CAIA mice. Endogenous CT signaling through the mammalian CTR has the potential to protect against joint inflammation, cartilage degradation, and excessive bone remodeling in experimental RA.

Keywords: Biological sciences; Immunology; Molecular biology.