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Article

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

1
Department of Internal Medicine 3 and Institute for Clinical Immunology, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
2
Division of Genetic Epidemiology and Division of Biological Chemistry, Innrain 80/IV, Medical University Innsbruck, 6020 Innsbruck, Austria
3
Department of Rheumatology, University Hospitals Birmingham NHS foundation trust, Edgbaston, B15 2GW Birmingham, UK
4
Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, Great Maze Pond, SE1 9RT London, UK
5
Division of Molecular Immunology of the Department of Internal Medicine 3, Ulmenweg 18, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Present address: Division of Biological Chemistry, Innrain 80/IV, Medical University Innsbruck, 6020 Innsbruck, Austria
Academic Editors: Chak-Sing Lau and Vera Sau-Fong Chan
Int. J. Mol. Sci. 2015, 16(8), 18825-18835; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160818825
Received: 30 June 2015 / Revised: 5 August 2015 / Accepted: 6 August 2015 / Published: 12 August 2015
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. View Full-Text
Keywords: osteoclastogenesis; mycophenolate mofetil; interferon alpha; systemic lupus erythematosus; RANKL osteoclastogenesis; mycophenolate mofetil; interferon alpha; systemic lupus erythematosus; RANKL
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MDPI and ACS Style

Fürnrohr, B.G.; Rhodes, B.; Munoz, L.E.; Weiß, K.; Vyse, T.J.; Schett, G. Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment. Int. J. Mol. Sci. 2015, 16, 18825-18835. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160818825

AMA Style

Fürnrohr BG, Rhodes B, Munoz LE, Weiß K, Vyse TJ, Schett G. Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment. International Journal of Molecular Sciences. 2015; 16(8):18825-18835. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160818825

Chicago/Turabian Style

Fürnrohr, Barbara G., Benjamin Rhodes, Luis E. Munoz, Katrin Weiß, Tim J. Vyse, and Georg Schett. 2015. "Osteoclast Differentiation Is Impaired in a Subgroup of SLE Patients and Correlates Inversely with Mycophenolate Mofetil Treatment" International Journal of Molecular Sciences 16, no. 8: 18825-18835. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160818825

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