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



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.



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.



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.
Department of Rheumatology and Inflammation Research, Centre for Bone and Arthritis Research (CBAR), Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30, Göteborg, Sweden. alexandra.stubelius@rheuma.gu.se.
Alexandra
A
Stubelius
Department of Rheumatology and Inflammation Research, Centre for Bone and Arthritis Research (CBAR), Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30, Göteborg, Sweden.
Annica
A
Andersson
Medical Inflammation Research, Karolinska Institutet, Stockholm, Sweden.
Rikard
R
Holmdahl
Department of Internal Medicine and Clinical nutrition, Centre for Bone and Arthritis Research (CBAR), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Claes
C
Ohlsson
Department of Rheumatology and Inflammation Research, Centre for Bone and Arthritis Research (CBAR), Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30, Göteborg, Sweden.
Ulrika
U
Islander
Department of Rheumatology and Inflammation Research, Centre for Bone and Arthritis Research (CBAR), Sahlgrenska Academy, University of Gothenburg, Box 480, 405 30, Göteborg, Sweden.
Hans
H
Carlsten
D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000276:immunology / Q000378:metabolism*; D015663:Osteoporosis, Postmenopausal / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010052:Ovariectomy; D017354:Point Mutation; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism
D004967:Estrogens; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
Bone mineral density; Estrogen Deficiency; NOX 2; Ncf1; Neutrophil cytosolic factor 1; Osteoclasts; Osteoimmunology; Postmenopausal bone loss; Pre-osteoclasts; Reactive Oxygen Species