caa a22 4500 605521352 CHVBK 20210128100739.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00223-015-9954-z doi (NATIONALLICENCE)springer-10.1007/s00223-015-9954-z High-Fat Diet Causes Bone Loss in Young Mice by Promoting Osteoclastogenesis Through Alteration of the Bone Marrow Environment [Elektronische Daten] [Lei Shu, Eric Beier, Tzong Sheu, Hengwei Zhang, Michael Zuscik, Edward Puzas, Brendan Boyce, Robert Mooney, Lianping Xing] Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12weeks. Decreased bone volume was detected after 3weeks of HFD treatment. After 6 and 12weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children. Springer Science+Business Media New York, 2015 HFD nationallicence Obesity nationallicence Bone volume nationallicence Osteoclasts nationallicence Precursor nationallicence Bone marrow nationallicence Shu Lei Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut Beier Eric Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut Sheu Tzong Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut Zhang Hengwei Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut Zuscik Michael Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut Puzas Edward Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut Boyce Brendan Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut Mooney Robert Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut Xing Lianping Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut Calcified Tissue International Springer US; http://www.springer-ny.com 96/4(2015-04-01), 313-323 0171-967X 96:4<313 2015 96 223 https://doi.org/10.1007/s00223-015-9954-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-9954-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shu Lei Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Beier Eric Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Sheu Tzong Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Zhang Hengwei Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Zuscik Michael Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Puzas Edward Center for Musculoskeletal Research, University of Rochester Medical Center, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Boyce Brendan Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Mooney Robert Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut NATIONALLICENCE 700 1- Xing Lianping Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, 14642, Rochester, NY, USA aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 96/4(2015-04-01), 313-323 0171-967X 96:4<313 2015 96 223