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Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis

Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarc...

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Autores principales: Kurowska, Weronika, Slowinska, Iwona, Krogulec, Zbigniew, Syrowka, Piotr, Maslinski, Wlodzimierz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073027/
https://www.ncbi.nlm.nih.gov/pubmed/33921836
http://dx.doi.org/10.3390/jcm10081778
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author Kurowska, Weronika
Slowinska, Iwona
Krogulec, Zbigniew
Syrowka, Piotr
Maslinski, Wlodzimierz
author_facet Kurowska, Weronika
Slowinska, Iwona
Krogulec, Zbigniew
Syrowka, Piotr
Maslinski, Wlodzimierz
author_sort Kurowska, Weronika
collection PubMed
description Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarce. We investigated whether ACPAs can contribute to osteoclast activation and bone erosion in RA bone marrow. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs), osteoclast activation indicators–the tartrate-resistant acid phosphatase 5b (TRAP5b) and cathepsin K, and bone degradation marker–C-terminal telopeptide of type I collagen (CTX-I) were measured in the bone marrow and peripheral blood of RA patients using ELISAs. We found that ACPAs present in RA bone marrow was associated with increased amounts of TRAP5b, cathepsin K and CTX-I in this location. Levels of IL-8, the key mediator of anti-citrullinated protein antibody (ACPA)-induced bone resorption, were also elevated in bone marrow containing anti-CCP Abs and positively correlated with TRAP5b and cathepsin K concentrations. Higher levels of TRAP5b, cathepsin K, CTX-I and IL-8 in bone marrow compared to peripheral blood indicate local generation of these molecules. Our results complement data from animal studies and highlight the relevance of ACPAs and bone marrow in bone resorption in RA.
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spelling pubmed-80730272021-04-27 Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis Kurowska, Weronika Slowinska, Iwona Krogulec, Zbigniew Syrowka, Piotr Maslinski, Wlodzimierz J Clin Med Article Normalizing bone metabolism is a challenge in rheumatoid arthritis (RA). Studies in mice suggest that anti-citrullinated protein antibodies (ACPAs) can trigger osteoclast activation and bone resorption in the bone marrow. However, data on the presence and role of ACPAs in human bone marrow are scarce. We investigated whether ACPAs can contribute to osteoclast activation and bone erosion in RA bone marrow. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs), osteoclast activation indicators–the tartrate-resistant acid phosphatase 5b (TRAP5b) and cathepsin K, and bone degradation marker–C-terminal telopeptide of type I collagen (CTX-I) were measured in the bone marrow and peripheral blood of RA patients using ELISAs. We found that ACPAs present in RA bone marrow was associated with increased amounts of TRAP5b, cathepsin K and CTX-I in this location. Levels of IL-8, the key mediator of anti-citrullinated protein antibody (ACPA)-induced bone resorption, were also elevated in bone marrow containing anti-CCP Abs and positively correlated with TRAP5b and cathepsin K concentrations. Higher levels of TRAP5b, cathepsin K, CTX-I and IL-8 in bone marrow compared to peripheral blood indicate local generation of these molecules. Our results complement data from animal studies and highlight the relevance of ACPAs and bone marrow in bone resorption in RA. MDPI 2021-04-19 /pmc/articles/PMC8073027/ /pubmed/33921836 http://dx.doi.org/10.3390/jcm10081778 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kurowska, Weronika
Slowinska, Iwona
Krogulec, Zbigniew
Syrowka, Piotr
Maslinski, Wlodzimierz
Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis
title Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis
title_full Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis
title_fullStr Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis
title_full_unstemmed Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis
title_short Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis
title_sort antibodies to citrullinated proteins (acpa) associate with markers of osteoclast activation and bone destruction in the bone marrow of patients with rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073027/
https://www.ncbi.nlm.nih.gov/pubmed/33921836
http://dx.doi.org/10.3390/jcm10081778
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