Loading...
Please wait, while we are loading the content...
Similar Documents
The Wnt Antagonist Secreted Frizzled-Related Protein-1 Is a Negative Regulator of Trabecular Bone Formation in Adult Mice
| Content Provider | Paperity |
|---|---|
| Author | Zhao, Weiguang Stein, Gary S. Komm, Barry S. Gaur, Tripti Kharode, Yogendra P. Lian, Jane B. Bodine, Peter V. N. Bex, Frederick J. Lambert, Andre-Jean Goad, Mary Beth |
| Abstract | Previous studies have associated activation of canonical Wnt signaling in osteoblasts with elevated bone formation. Here we report that deletion of the murine Wnt antagonist, secreted frizzled-related protein (sFRP)-1, prolongs and enhances trabecular bone accrual in adult animals. sFRP-1 mRNA was expressed in bones and other tissues of +/+ mice but was not observed in −/− animals. Despite its broad tissue distribution, ablation of sFRP-1 did not affect blood and urine chemistries, most nonskeletal organs, or cortical bone. However, sFRP-1−/− mice exhibited increased trabecular bone mineral density, volume, and mineral apposition rate when compared with +/+ controls. The heightened trabecular bone mass of sFRP-1−/− mice was observed in adult animals between the ages of 13–52 wk, occurred in multiple skeletal sites, and was seen in both sexes. Mechanistically, loss of sFRP-1 reduced osteoblast and osteocyte apoptosis in vivo. In addition, deletion of sFRP-1 inhibited osteoblast lineage cell apoptosis while enhancing the proliferation and differentiation of these cells in vitro. Ablation of sFRP-1 also increased osteoclastogenesis in vitro, although changes in bone resorption were not observed in intact animals in vivo. Our findings demonstrate that deletion of sFRP-1 preferentially activates Wnt signaling in osteoblasts, leading to enhanced trabecular bone formation in adults. |
| Starting Page | 1222 |
| Ending Page | 1237 |
| File Format | HTM / HTML |
| ISSN | 08888809 |
| DOI | 10.1210/me.2003-0498 |
| Issue Number | 5 |
| Journal | Molecular Endocrinology |
| Volume Number | 18 |
| e-ISSN | 19449917 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2004-05-01 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Endocrinology |
