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Abstract
Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in osteoporosis development has previously been investigated using various methods to inhibit IL-17A signaling in this model. However, the studies show opposing results. While some publications reported IL-17A as a mediator of OVX-induced osteoporosis, others found a bone-protective role for IL-17 receptor signaling. In this study, we provide an explanation for the discrepancies in previous literature and show for the first time that loss of IL-17A has differential effects on OVX-induced osteoporosis; with IL-17A being important for cortical but not trabecular bone loss. Interestingly, the decrease in trabecular bone after OVX in IL-17A knock-out mice, was accompanied by increased adipogenesis depicted by elevated leptin levels. Additionally, the bone marrow adipose tissue expanded, and the bone-turnover decreased in ovariectomized mice lacking IL-17A compared to ovariectomized WT mice. Our results increase the understanding of how IL-17A signaling influences bone remodeling in the different bone compartments, which is of importance for the development of new treatments of post-menopausal osteoporosis.
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1 Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582)
2 Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582)
3 Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582)
4 Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (GRID:grid.143643.7) (ISNI:0000 0001 0660 6861)
5 Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582)
6 Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); Department of Drug Treatment, Sahlgrenska University Hospital, Gothenburg, Sweden (GRID:grid.1649.a) (ISNI:000000009445082X)