Clare E Yellowley1, Damian C Genetos2. 1. Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA. 2. Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, 1089 Veterinary Medicine Drive, Davis, CA, 95616, USA. dgenetos@ucdavis.edu.
Abstract
PURPOSE OF REVIEW: We reviewed recent literature on oxygen sensing in osteogenic cells and its contribution to development of a skeletal phenotype, the coupling of osteogenesis with angiogenesis and integration of hypoxia into canonical Wnt signaling, and opportunities to manipulate oxygen sensing to promote skeletal repair. RECENT FINDINGS: Oxygen sensing in osteocytes can confer a high bone mass phenotype in murine models; common and unique targets of HIF-1α and HIF-2α and lineage-specific deletion of oxygen sensing machinery suggest differentia utilization and requirement of HIF-α proteins in the differentiation from mesenchymal stem cell to osteoblast to osteocyte; oxygen-dependent but HIF-α-independent signaling may contribute to observed skeletal phenotypes. Manipulating oxygen sensing machinery in osteogenic cells influences skeletal phenotype through angiogenesis-dependent and angiogenesis-independent pathways and involves HIF-1α, HIF-2α, or both proteins. Clinically, an FDA-approved iron chelator promotes angiogenesis and osteogenesis, thereby enhancing the rate of fracture repair.
PURPOSE OF REVIEW: We reviewed recent literature on oxygen sensing in osteogenic cells and its contribution to development of a skeletal phenotype, the coupling of osteogenesis with angiogenesis and integration of hypoxia into canonical Wnt signaling, and opportunities to manipulate oxygen sensing to promote skeletal repair. RECENT FINDINGS:Oxygen sensing in osteocytes can confer a high bone mass phenotype in murine models; common and unique targets of HIF-1α and HIF-2α and lineage-specific deletion of oxygen sensing machinery suggest differentia utilization and requirement of HIF-α proteins in the differentiation from mesenchymal stem cell to osteoblast to osteocyte; oxygen-dependent but HIF-α-independent signaling may contribute to observed skeletal phenotypes. Manipulating oxygen sensing machinery in osteogenic cells influences skeletal phenotype through angiogenesis-dependent and angiogenesis-independent pathways and involves HIF-1α, HIF-2α, or both proteins. Clinically, an FDA-approved iron chelator promotes angiogenesis and osteogenesis, thereby enhancing the rate of fracture repair.
Authors: Longze Zhang; Tao Wang; Martin Chang; Claire Kaiser; Jason D Kim; Tianyu Wu; Xiaoyi Cao; Xinping Zhang; Edward M Schwarz Journal: J Bone Miner Res Date: 2017-07-19 Impact factor: 6.741
Authors: Peter V N Bodine; Weiguang Zhao; Yogendra P Kharode; Frederick J Bex; Andre-Jean Lambert; Mary Beth Goad; Tripti Gaur; Gary S Stein; Jane B Lian; Barry S Komm Journal: Mol Endocrinol Date: 2004-02-19
Authors: Stacy H Shomento; Chao Wan; Xuemei Cao; Marie-Claude Faugere; Mary L Bouxsein; Thomas L Clemens; Ryan C Riddle Journal: J Cell Biochem Date: 2010-01-01 Impact factor: 4.429
Authors: Colleen Wu; Erinn B Rankin; Laura Castellini; Javier F Alcudia; Javier Fernandez-Alcudia; Edward L LaGory; Rebecca Andersen; Steven D Rhodes; Tremika L S Wilson; Khalid S Mohammad; Alesha B Castillo; Theresa A Guise; Ernestina Schipani; Amato J Giaccia Journal: Genes Dev Date: 2015-04-06 Impact factor: 11.361
Authors: Kevin Schilling; Mirna El Khatib; Shane Plunkett; Jiajia Xue; Younan Xia; Sergei A Vinogradov; Edward Brown; Xinping Zhang Journal: ACS Appl Mater Interfaces Date: 2019-09-04 Impact factor: 9.229
Authors: Jingyi Xu; Xing Qiu; Gary Yu; Maria Ly; Jun Yang; Rona M Silva; Xun Zhang; Mang Yu; Yinong Wang; Bruce Hammock; Kent E Pinkerton; Dewei Zhao Journal: Toxicology Date: 2021-11-18 Impact factor: 4.571
Authors: Lisa B Matlen; Daniel G Whitney; Daniel Whibley; Erica C Jansen; Ronald D Chervin; Galit Levi Dunietz Journal: J Clin Sleep Med Date: 2021-09-01 Impact factor: 4.324