Proinflammatory and bone protective role of calcitonin gene-related peptide alpha in collagen antibody-induced arthritis

Authors
T Maleitzke, A Hildebrandt, J Weber, et al

Lab
Center for Musculoskeletal Surgery, CharitŽ - UniversitŠtsmedizin Berlin, Berlin, Germany

Journal
Reumatalogy

Abstract
Objectives: Calcitonin gene-related peptide alpha (alphaCGRP) represents an immunomodulatory neuropeptide implicated in pain perception. alphaCGRP also functions as a critical regulator of bone formation and is overexpressed in patients with rheumatoid arthritis (RA). In the present study, we investigated the role of alphaCGRP in experimental RA regarding joint inflammation and bone remodelling.
Methods: Collagen II-antibody-induced arthritis (CAIA) was induced in wild type (WT) and alphaCGRP-deficient (_CGRP-/-) mice. Animals were monitored over 10 and 48 days with daily assessments of the semiquantitative arthritis score and grip strength test. Joint inflammation, cartilage degradation and bone erosions were assessed by histology, gene expression analysis and microCT.
Results: CAIA was accompanied by an overexpression of alphaCGRP in WT joints. alphaCGRP-/- mice displayed reduced arthritic inflammation and cartilage degradation. Congruently, the expression of TNF-alpha, IL-1beta, CD80 and MMP13 was induced in WT, but not alphaCGRP-/- animals. WT mice displayed an increased bone turnover during the acute inflammatory phase, which was not the case in alphaCGRP-/- mice. Interestingly, WT mice displayed a full recovery from the inflammatory bone disease, whereas alphaCGRP-/- mice exhibited substantial bone loss over time.
Conclusion: This study demonstrates a proinflammatory and bone protective role of alphaCGRP in CAIA. Our data indicate that alphaCGRP not only enhances joint inflammation, but also controls bone remodelling as part of arthritis resolution. As novel alphaCGRP inhibitors are currently introduced clinically for the treatment of migraine, their potential impact on RA progression warrants further clinical investigation.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)