Artikel
Bone Sparing and Anti-Inflammatory Effects of the Calcitonin Receptor in Collagen Antibody-Induced Arthritis
Suche in Medline nach
Autoren
Veröffentlicht: | 26. Oktober 2021 |
---|
Gliederung
Text
Objectives: Calcitonin (CT), a calcium regulatory hormone, and its receptor (CTR) play an indispensable role in bone and joint integrity. Bone protective and anti-resorptive properties of CT derived from eel or salmon have therefore been successfully employed to treat bone lesions and alleviate pain in patients suffering from rheumatoid arthritis (RA) and osteoarthritis. While teleost CT is known to inhibit osteoclast activity and cartilage degradation, effects of endogenous CT and the CTR in inflammatory joint diseases remains speculative. With this study we strive to unravel the role of the CTR in joint inflammation, cartilage and bone homeostasis in a murine model of antibody-mediated arthritis.
Methods: CTR-deficient (Calcr-/-) (n=15) and wild type (WT) (n=13) mice were challenged with collagen II-antibody-induced arthritis (CAIA), while Calcr-/- control (CTRL) (n=8) and WT CTRL (n=8) animals received phosphate-buffered saline. Animals were monitored daily, employing the semiquantitative clinical arthritis score and end points were set at day 10 and 48. Articular inflammation, cartilage degradation and bone alterations were assessed by histology, histomorphometry, gene expression analysis and µ-computed tomography.
Results and Conclusion: Full arthritic phenotypes were developed by Calcr-/- CAIA and WT CAIA animals with no differences between groups according to the clinical arthritis score. Intraarticular inflammation and cartilage degradation were histologically present in both groups, yet more pronounced in Calcr-/- CAIA mice. Inflammatory and immunomodulatory markers, including TNF-alpha and CD80 were upregulated again in both groups, however TGF-beta, IL-1-beta, CD14, CD68, CCL-2 and SPHK1 were only increased in Calcr-/- CAIA animals compared to CTRL mice during the acute phase of CAIA. Bone integrity was markedly impaired in Calcr-/- CAIA mice at day 48 with a substantial loss in bone volume, bone density, bone surface and trabecular number, a development not observed in WT CAIA animals.
For the first time, this study unveils an anti-inflammatory and bone and cartilage protective role of the CTR in a murine model of experimental RA. Intact CT signalling appears to be crucial for the containment of inflammation and restoration and maintenance of bone integrity during inflammatory joint diseases.