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Ncf1 affects osteoclast formation but is not critical for postmenopausal bone loss

Journal article
Authors Alexandra Stubelius
Annica Andersson
R. Holmdahl
Claes Ohlsson
Ulrika Islander
Hans Carlsten
Published in BMC Musculoskeletal Disorders
Volume 17
Issue 1
Pages 1-7
ISSN 1471-2474
Publication year 2016
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 1-7
Language en
Links dx.doi.org/10.1186/s12891-016-1315-...
Keywords Bone mineral density, Estrogen Deficiency, Ncf1, Neutrophil cytosolic factor 1, NOX 2, Osteoclasts, Osteoimmunology, Postmenopausal bone loss, Pre-osteoclasts, Reactive Oxygen Species
Subject categories Rheumatology and Autoimmunity, Immunology in the medical area

Abstract

Background: Increased reactive oxygen species and estrogen deficiency contribute to the pathophysiology of postmenopausal osteoporosis. Reactive oxygen species contribute to bone degradation and is necessary for RANKL-induced osteoclast differentiation. In postmenopausal bone loss, reactive oxygen species can also activate immune cells to further enhance bone resorption. Here, we investigated the role of reactive oxygen species in ovariectomy-induced osteoporosis in mice deficient in Ncf1, a subunit for the NADPH oxidase 2 and a well-known regulator of the immune system. Methods: B10.Q wild-type (WT) mice and mice with a spontaneous point mutation in the Ncf1-gene (Ncf1*/*) were ovariectomized (ovx) or sham-operated. After 4 weeks, osteoclasts were generated ex vivo, and bone mineral density was measured using peripheral quantitative computed tomography. Lymphocyte populations, macrophages, pre-osteoclasts and intracellular reactive oxygen species were analyzed by flow cytometry. Results: After ovx, Ncf1*/*-mice formed fewer osteoclasts ex vivo compared to WT mice. However, trabecular bone mineral density decreased similarly in both genotypes after ovx. Ncf1*/*-mice had a larger population of pre-osteoclasts, whereas lymphocytes were activated to the same extent in both genotypes. Conclusion: Ncf1*/*-mice develop fewer osteoclasts after ovx than WT mice. However, irrespective of genotype, bone mineral density decreases after ovx, indicating that a compensatory mechanism retains bone degradation after ovx. © 2016 The Author(s).

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