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Adequate hypoxia inducible factor 1α signaling is indispensable for bone regeneration
- Source :
- Bone. 87:176-186
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Engineered cell-based constructs are an appealing strategy to treat large skeletal defects. However, transplanted cells are often confronted with an environment that is deprived of oxygen and nutrients. Upon hypoxia, most cell types activate hypoxia-inducible factor 1α (HIF-1α) signaling, but its importance for implanted osteoprogenitor cells during bone regeneration is not elucidated. To this end, we specifically deleted the HIF--1α isoform in periosteal progenitor cells and show that activation of HIF-1α signaling in these cells is critical for bone repair by modulating angiogenic and metabolic processes. Activation of HIF-1α is not only crucial for blood vessel invasion, by enhancing angiogenic growth factor production, but also for periosteal cell survival early after implantation, when blood vessels have not yet invaded the construct. HIF-1α signaling limits oxygen consumption to avoid accumulation of harmful ROS and preserve redox balance, and additionally induces a switch to glycolysis to prevent energetic distress. Altogether, our results indicate that the proangiogenic capacity of implanted periosteal cells is HIF-1α regulated and that metabolic adaptations mediate post-implantation cell survival.
- Subjects :
- 0301 basic medicine
Cell type
Bone Regeneration
Histology
Cell Survival
Physiology
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Cell
Neovascularization, Physiologic
Biology
Regenerative medicine
03 medical and health sciences
0302 clinical medicine
Periosteum
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Progenitor cell
Bone regeneration
Growth factor
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Cell Hypoxia
Cell biology
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Hypoxia-inducible factors
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Immunology
medicine.symptom
Energy Metabolism
Reactive Oxygen Species
Glycolysis
Gene Deletion
Subjects
Details
- ISSN :
- 87563282
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Bone
- Accession number :
- edsair.doi.dedup.....8180b5a848585ff59808cdf8dc0abc98