Journal
JBMR PLUS
Volume 4, Issue 6, Pages -Publisher
WILEY
DOI: 10.1002/jbm4.10364
Keywords
ADIPOCYTE; BONE MARROW ADIPOSITY; BONE MASS; DICKKOPF-1; HIGH-FAT DIET; OSTEOBLAST
Categories
Funding
- European Union's Horizon 2020 research and innovation program under the MARIE SKLODOWSKA-CURIE grant [860898]
- Meddrive grant from the Medical Faculty of the Technische Universitat Dresden
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Low bone strength in overweight individuals is a significant medical problem. One important determinant of mesenchymal stem cell fate into osteoblasts or adipocytes is the Wnt signaling pathway. We recently showed that Dickkopf-1 (DKK1), a potent Wnt inhibitor, is upregulated in obese mice. In this study, we investigated the role of DKK1 in the pathogenesis of obesity-induced bone loss using global and tissue-specific KO mice. Obesity was induced in 8-week-old male mice with an inducible global (Rosa26-CreERT2) or osteoprogenitor- (Osx-Cre-) specific deletion of Dkk1 with a high-fat diet (HFD) containing 60% fat. After 12 weeks, body weight, bone volume, bone fat mass, and bone turnover were assessed. Dkk1(fl/fl);Rosa26-CreERT2 mice experienced a similar increase in body weight and white fat pads as control mice. A HFD significantly reduced trabecular bone mass and the bone formation rate in Cremice and Dkk1(fl/fl);Rosa26-CreERT2 mice. Interestingly, Dkk1(fl/fl);Rosa26-CreERT2 mice were protected from HFD-induced cortical bone loss. Furthermore, a HFD was associated with increased bone marrow fat in the femur, which was less pronounced in Dkk1(fl/fl); Rosa26-CreERT2 mice. Mice with an osteoprogenitor-specific Dkk1 deletion showed similar results as the global knockout, showing a protection against HFD-induced cortical bone loss and an accumulation of bone marrow fat, but a similar decrease in trabecular bone volume. In summary, DKK1 appears to contribute distinctly to cortical, but not trabecular bone loss in obesity. (C) 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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