Abstract
BackgroundIncreased 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.MethodsB10.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.ResultsAfter 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.ConclusionNcf1*/*-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.
Highlights
Increased reactive oxygen species and estrogen deficiency contribute to the pathophysiology of postmenopausal osteoporosis
We found that bone mineral density decreased to the same extent in both Neutrophil cytosolic factor 1 (Ncf1)-deficient mice and wild type (WT) mice, the OCL formation and preosteoclast populations were differentially affected in the two genotypes
Osteoclastogenesis increases after ovx in WT mice but not in Ncf1*/*-mice Osteoclastogenesis was induced from bone marrow cells
Summary
Increased reactive oxygen species and estrogen deficiency contribute to the pathophysiology of postmenopausal osteoporosis. Reactive oxygen species can activate immune cells to further enhance bone resorption. We investigated the role of reactive oxygen species in ovariectomyinduced osteoporosis in mice deficient in Ncf, a subunit for the NADPH oxidase 2 and a well-known regulator of the immune system. Osteoclasts (OCL) resorb bone, and the presence of reactive oxygen species (ROS) at the interface between OCL and bone suggests a role for ROS in bone resorption [1,2,3,4]. To investigate the role of ROS and Ncf in postmenopausal bone loss, we employed a postmenopausal boneloss model by ovx or sham operating mice with a spontaneous mutation in Ncf.
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