Osteocyte hypoxia: a novel mechanotransduction pathway. Am. J. Physiol. 277
(Cell Physiol. 46): C598-C602, 1999.-Bone is a unique tissue in which to e
xamine mechanotransduction due to its essential role in weight bearing. Wit
hin bone, the osteocyte is an ideal cellular mechanotransducer candidate. B
ecause osteocytes reside distant from the blood supply, their metabolic nee
ds are met by a combination of passive diffusion and enhanced diffusion, ar
ising when the tissue is loaded during functional activity. Therefore, we h
ypothesized that depriving a bone of mechanical loading (and thus eliminati
ng diffusion enhanced by loading) would rapidly induce osteocyte hypoxia. U
sing the avian ulna model of disuse osteopenia, we found that 24 h of unloa
ding results in significant osteocyte hypoxia (8.4 +/- 1.8%) compared with
control levels (1.1 +/- 0.5%; P = 0.03). Additionally, we present prelimina
ry data suggesting that a brief loading regimen is sufficient to rescue ost
eocytes from this fate. The rapid onset of the observed osteocyte hypoxia,
the inhibition of hypoxia by brief loading, and the cellular consequences o
f oxygen deprivation are suggestive of a novel mechanotransduction pathway
with implications across organ systems.