| First Author | Tomlinson RE | Year | 2015 |
| Journal | Bone | Volume | 73 |
| Pages | 98-104 | PubMed ID | 25541207 |
| Mgi Jnum | J:220899 | Mgi Id | MGI:5637445 |
| Doi | 10.1016/j.bone.2014.12.015 | Citation | Tomlinson RE, et al. (2015) HIF-1alpha regulates bone formation after osteogenic mechanical loading. Bone 73:98-104 |
| abstractText | HIF-1 is a transcription factor typically associated with angiogenic gene transcription under hypoxic conditions. In this study, mice with HIF-1alpha deleted in the osteoblast lineage (DeltaHIF-1alpha) were subjected to damaging or non-damaging mechanical loading known to produce woven or lamellar bone, respectively, at the ulnar diaphysis. By microCT, DeltaHIF-1alpha mice produced significantly less woven bone than wild type (WT) mice 7days after damaging loading. This decrease in woven bone volume and extent was accompanied by a significant decrease in vascularity measured by immunohistochemistry against vWF. Additionally, osteocytes, rather than osteoblasts, appear to be the main bone cell expressing HIF-1alpha following damaging loading. In contrast, 10days after non-damaging mechanical loading, dynamic histomorphometry measurements demonstrated no impairment in loading-induced lamellar bone formation in DeltaHIF-1alpha mice. In fact, both non-loaded and loaded ulnae from DeltaHIF-1alpha mice had increased bone formation compared with WT ulnae. When comparing the relative increase in periosteal bone formation in loaded vs. non-loaded ulnae, it was not different between DeltaHIF-1alpha mice and controls. There were no significant differences observed between WT and DeltaHIF-1alpha mice in endosteal bone formation parameters. The increases in periosteal lamellar bone formation in DeltaHIF-1alpha mice are attributed to non-angiogenic effects of the knockout. In conclusion, these results demonstrate that HIF-1alpha is a pro-osteogenic factor for woven bone formation after damaging loading, but an anti-osteogenic factor for lamellar bone formation under basal conditions and after non-damaging loading. |
