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Cortical Bone Loss in a Spontaneous Murine Model of Systemic Lupus Erythematosus

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Abstract

Patients with systemic lupus erythematosus (SLE), a chronic inflammatory disease characterized by loss of T- and B-cell tolerance to autoantigens, are at increased risk for osteoporosis and fractures. Mice deficient in Fc gamma receptor IIb (FcγRIIB) exhibit spontaneous SLE and its restoration rescues the disease. To determine whether deleting FcγRIIB affects cortical bone mass and mechanical properties, we analyzed cortical bone phenotype of FcγRIIB knockouts at different ages. FACS analysis revealed that 6-month-old FcγRIIB−/− mice had increased B220lowCD138+ cells, markers of plasma cells, indicating active SLE disease. In contrast, 3-month-old FcγRIIB−/− mice did not develop the active SLE disease. µCT analysis indicated that FcγRIIB deletion did not affect cortical bone in 3-month-old mutants. However, 6- and 10-month-old FcγRIIB−/− males and females had osteopenic cortical bone and the severity of bone loss increased with disease duration. FcγRIIB deletion decreased cross-sectional area, cortical area, and marrow area in 6-month-old males. Cortical area and cortical thickness were decreased in 10-month-old FcγRIIB−/− males. Lack of FcγRIIB decreased cortical thickness without affecting cortical area in females. However, deletion of a single FcγRIIB allele was insufficient to induce cortical bone loss. The bending strength was decreased in 6- and 10-month-old FcγRIIB-deficient males compared to WT controls. A microindentation analysis demonstrated significantly decreased hardness in both 10-month-old FcγRIIB−/− males and females. Our data indicate that FcγRIIB contributes to the regulation of cortical bone homeostasis subsequent to SLE development and that deletion of FcγRIIB in mice leads to SLE-like disease associated with cortical bone loss and decreased bending strength and hardness.

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Acknowledgements

We thank Anucharte Srijunbarl for his suggestion about microindentation and Dr. Kevin Tompkins for his critical reading of the manuscript.

Funding

This research was funded by the Ratchadapisek Sompoch Endowment Fund (2014), Chulalongkorn University (CU-57-091-IC), and the Faculty of Dentistry, Chulalongkorn University (DRF 61019) to S. Lotinun.

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Authors and Affiliations

  1. Department of Physiology and Skeletal Disorders Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

    Worasit Saiworn, Peerapat Visitchanakun, Korakot Atjanasuppat, Jiratha Chantaraaumporn, Jutarat Mokdara, Sirintra Chungchatupornchai & Sutada Lotinun

  2. Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand

    Arthid Thim-uam

  3. Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Prapaporn Pisitkun

  4. Division of Immunology, Department of Microbiology, Faculty of Medicine, and Skeletal Disorders Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

    Asada Leelahavanichkul

  5. Department of Prosthodontics and Skeletal Disorders Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

    Suchit Poolthong

  6. Division of Bone and Mineral Research, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA

    Roland Baron

  7. Harvard Medical School, Department of Medicine, Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA

    Roland Baron

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  1. Worasit Saiworn
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Correspondence to Sutada Lotinun.

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Conflict of interest

Worasit Saiworn, Arthid Thim-uam, Peerapat Visitchanakun, Korakot Atjanasuppat, Jiratha Chantaraaumporn, Jutarat Mokdara, Sirintra Chungchatupornchai, Prapaporn Pisitkun, Asada Leelahavanichkul, Suchit Poolthong, Roland Baron, and Sutada Lotinun declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The animals were housed at the Faculty of Medicine, Chulalongkorn University and maintained in accordance with the Guide for the Care and Use of Laboratory Animals (eight edition), National Research Council. All procedures were approved by the Institutional Animal Care and Use Committee at Faculty of Medicine, Chulalongkorn University.

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Saiworn, W., Thim-uam, A., Visitchanakun, P. et al. Cortical Bone Loss in a Spontaneous Murine Model of Systemic Lupus Erythematosus. Calcif Tissue Int 103, 686–697 (2018). https://doi.org/10.1007/s00223-018-0464-7

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