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
Affiliations
Tazio Maleitzke
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, 10178 Berlin, Germany
Alexander Hildebrandt
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Tamara Dietrich
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Jessika Appelt
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Denise Jahn
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Ellen Otto
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Dario Zocholl
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biometry and Clinical Epidemiology, 10117 Berlin, Germany
Anke Baranowsky
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany
Georg N. Duda
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Serafeim Tsitsilonis
Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, 13353 Berlin, Germany; Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Julius Wolff Institute, 13353 Berlin, Germany
Johannes Keller
Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, 10178 Berlin, Germany; Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany; Corresponding author
Summary: 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.
