Proinflammatory and bone protective role of calcitonin gene-related peptide alpha in collagen antibody-induced arthritis
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Proinflammatory and bone protective role of calcitonin gene-related peptide alpha in collagen antibody-induced arthritis. / Maleitzke, Tazio; Hildebrandt, Alexander; Weber, Jérôme; Dietrich, Tamara; Appelt, Jessika; Jahn, Denise; Zocholl, Dario; Baranowsky, Anke; Duda, Georg N; Tsitsilonis, Serafeim; Keller, Johannes.
in: RHEUMATOLOGY, Jahrgang 60, Nr. 4, 06.04.2021, S. 1996-2009.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Proinflammatory and bone protective role of calcitonin gene-related peptide alpha in collagen antibody-induced arthritis
AU - Maleitzke, Tazio
AU - Hildebrandt, Alexander
AU - Weber, Jérôme
AU - Dietrich, Tamara
AU - Appelt, Jessika
AU - Jahn, Denise
AU - Zocholl, Dario
AU - Baranowsky, Anke
AU - Duda, Georg N
AU - Tsitsilonis, Serafeim
AU - Keller, Johannes
N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2021/4/6
Y1 - 2021/4/6
N2 - OBJECTIVES: Calcitonin gene-related peptide alpha (αCGRP) represents an immunomodulatory neuropeptide implicated in pain perception. αCGRP 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 αCGRP in experimental RA regarding joint inflammation and bone remodelling.METHODS: Collagen II-antibody-induced arthritis (CAIA) was induced in wild type (WT) and αCGRP-deficient (αCGRP-/-) 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 µCT.RESULTS: CAIA was accompanied by an overexpression of αCGRP in WT joints. αCGRP-/- mice displayed reduced arthritic inflammation and cartilage degradation. Congruently, the expression of TNF-α, IL-1β, CD80 and MMP13 was induced in WT, but not αCGRP-/- animals. WT mice displayed an increased bone turnover during the acute inflammatory phase, which was not the case in αCGRP-/- mice. Interestingly, WT mice displayed a full recovery from the inflammatory bone disease, whereas αCGRP-/- mice exhibited substantial bone loss over time.CONCLUSION: This study demonstrates a proinflammatory and bone protective role of αCGRP in CAIA. Our data indicate that αCGRP not only enhances joint inflammation, but also controls bone remodelling as part of arthritis resolution. As novel αCGRP inhibitors are currently introduced clinically for the treatment of migraine, their potential impact on RA progression warrants further clinical investigation.
AB - OBJECTIVES: Calcitonin gene-related peptide alpha (αCGRP) represents an immunomodulatory neuropeptide implicated in pain perception. αCGRP 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 αCGRP in experimental RA regarding joint inflammation and bone remodelling.METHODS: Collagen II-antibody-induced arthritis (CAIA) was induced in wild type (WT) and αCGRP-deficient (αCGRP-/-) 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 µCT.RESULTS: CAIA was accompanied by an overexpression of αCGRP in WT joints. αCGRP-/- mice displayed reduced arthritic inflammation and cartilage degradation. Congruently, the expression of TNF-α, IL-1β, CD80 and MMP13 was induced in WT, but not αCGRP-/- animals. WT mice displayed an increased bone turnover during the acute inflammatory phase, which was not the case in αCGRP-/- mice. Interestingly, WT mice displayed a full recovery from the inflammatory bone disease, whereas αCGRP-/- mice exhibited substantial bone loss over time.CONCLUSION: This study demonstrates a proinflammatory and bone protective role of αCGRP in CAIA. Our data indicate that αCGRP not only enhances joint inflammation, but also controls bone remodelling as part of arthritis resolution. As novel αCGRP inhibitors are currently introduced clinically for the treatment of migraine, their potential impact on RA progression warrants further clinical investigation.
U2 - 10.1093/rheumatology/keaa711
DO - 10.1093/rheumatology/keaa711
M3 - SCORING: Journal article
C2 - 33221885
VL - 60
SP - 1996
EP - 2009
JO - RHEUMATOLOGY
JF - RHEUMATOLOGY
SN - 1462-0324
IS - 4
ER -