Osteocyte hypoxia: a novel mechanotransduction pathway.
Bone is a unique tissue in which to examine mechanotransduction due to its essential role in weight bearing. Within bone, the osteocyte is an ideal cellular mechanotransducer candidate. Because osteocytes reside distant from the blood supply, their metabolic needs are met by a combination of passive diffusion and enhanced diffusion, arising when the tissue is loaded during functional activity. Therefore, we hypothesized that depriving a bone of mechanical loading (and thus eliminating diffusion enhanced by loading) would rapidly induce osteocyte hypoxia. Using the avian ulna model of disuse osteopenia, we found that 24 h of unloading results in significant osteocyte hypoxia (8.4 +/- 1.8%) compared with control levels (1.1 +/- 0.5%; P = 0.03). Additionally, we present preliminary data suggesting that a brief loading regimen is sufficient to rescue osteocytes from this fate. The rapid onset of the observed osteocyte hypoxia, the inhibition of hypoxia by brief loading, and the cellular consequences of oxygen deprivation are suggestive of a novel mechanotransduction pathway with implications across organ systems.
Dodd
J S
JS
Department of Orthopaedic Surgery, University of Cincinnati, Cincinnati, Ohio 45267-0212, USA.
Raleigh
J A
JA
Gross
T S
TS
D000818:Animals; D001696:Biomechanical Phenomena; D015687:Cell Hypoxia / Q000502:physiology*; D006706:Homeostasis; D008297:Male; D010011:Osteocytes / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D014422:Turkeys; D014457:Ulna / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology
D010100:Oxygen