Effects of orbital spaceflight on human osteoblastic cell physiology and gene expression

During long-term spaceflight, astronauts lose bone, in part due to a reduct ion in bone formation. It is not clear, however, whether the force imparted by gravity has direct effects on bone cells. To examine the response of bo ne forming cells to weightlessness, human fetal osteoblastic (hFOB) cells w ere cultured during the 17 day STS-80 space shuttle mission. Fractions of c onditioned media were collected during flight and shortly after landing for analyses of glucose utilization and accumulation of type I collagen and pr ostaglandin E-2 (PGE(2)). Total cellular RNA was isolated from night and gr ound control cultures after landing. Measurement of glucose levels in condi tioned media indicated that glucose utilization occurred at a similar rate in night and ground control cultures, Furthermore, the levels of type I col lagen and PGE(2) accumulation in the flight and control conditioned media w ere indistinguishable. The steady-state levels of osteonectin, alkaline pho sphatase, and osteocalcin messenger RNA (mRNA) were not significantly chang ed following space-flight. Gene-specific reductions in mRNA levels for cyto kines and skeletal growth factors were detected in the night cultures using RNase protection assays. Steady-state mRNA levels for interleukin (IL)-1 a lpha and IL-6 were decreased 8 h following the night and returned to contro l levels at 24 h postflight. Also, transforming growth factor (TGF)-beta(2) and TGF-beta(1) message levels were modestly reduced at 8 h and 24 h postf light, although the change was not statistically significant at 8 h, These data suggest that spaceflight did not significantly affect hFOB cell prolif eration, expression of type I collagen, or PGE(2) production, further sugge sting that the removal of osteoblastic cells from the context of the bone t issue results in a reduced ability to respond to weightlessness. However, s paceflight followed by return to earth significantly impacted the expressio n of cytokines and skeletal grow th factors, which have been implicated as mediators of the bone remodeling cycle. It is not yet clear whether these l atter changes were due to weightlessness or to the transient increase in lo ading resulting from reentry. (Bone 26:325-331; 2000) (C) 2000 by Elsevier Science Inc. All rights reserved.