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Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment

Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteocl...

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Autores principales: Fürnrohr, Barbara G., Rhodes, Benjamin, Munoz, Luis E., Weiß, Katrin, Vyse, Tim J., Schett, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581274/
https://www.ncbi.nlm.nih.gov/pubmed/26274951
http://dx.doi.org/10.3390/ijms160818825
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author Fürnrohr, Barbara G.
Rhodes, Benjamin
Munoz, Luis E.
Weiß, Katrin
Vyse, Tim J.
Schett, Georg
author_facet Fürnrohr, Barbara G.
Rhodes, Benjamin
Munoz, Luis E.
Weiß, Katrin
Vyse, Tim J.
Schett, Georg
author_sort Fürnrohr, Barbara G.
collection PubMed
description Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4–89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-α (IFNα) and -γ (IFNγ) we measured serum IFNα and IFNγ levels. Patients with very low osteoclast counts also had comparably higher IFNα serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNα serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect.
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spelling pubmed-45812742015-09-28 Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment Fürnrohr, Barbara G. Rhodes, Benjamin Munoz, Luis E. Weiß, Katrin Vyse, Tim J. Schett, Georg Int J Mol Sci Article Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4–89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-α (IFNα) and -γ (IFNγ) we measured serum IFNα and IFNγ levels. Patients with very low osteoclast counts also had comparably higher IFNα serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNα serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect. MDPI 2015-08-12 /pmc/articles/PMC4581274/ /pubmed/26274951 http://dx.doi.org/10.3390/ijms160818825 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fürnrohr, Barbara G.
Rhodes, Benjamin
Munoz, Luis E.
Weiß, Katrin
Vyse, Tim J.
Schett, Georg
Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment
title Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment
title_full Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment
title_fullStr Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment
title_full_unstemmed Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment
title_short Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment
title_sort osteoclast differentiation is impaired in a subgroup of sle patients and correlates inversely with mycophenolate mofetil treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581274/
https://www.ncbi.nlm.nih.gov/pubmed/26274951
http://dx.doi.org/10.3390/ijms160818825
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