MICROGRAVITY INDUCES PROSTAGLANDIN E(2) AND INTERLEUKIN-6 PRODUCTION IN NORMAL RAT OSTEOBLASTS - ROLE IN BONE DEMINERALIZATION

It has been suggested that microgravity alters bone metabolism. Eviden ce for this phenomenon includes the negative calcium balance and decre ased bone density in astronauts, as well as, inhibition of bone format ion in rats flown for 2 to 3 weeks. However, the specific mechanisms t hat modulate these changes in microgravity are unknown. The purpose of this study was to clarify the mechanism of microgravity-induced bone demineralization using normal rat osteoblasts obtained from femur marr ow cultures. The osteoblasts were cultured for 5 days during a Shuttle -Spacelab flight (STS-65), After collection of the culture medium, the cellular DNA and RNA were fixed on board. Enzyme-immunoassay of the c ulture medium for prostaglandin E2 (PGE2) indicated that microgravity induced a 4.5- to 136-fold increase in flight samples as compared to t he ground control cultures, This increase of PGE2 production was consi stent with a 3.3- to 9.5-fold elevation of inducible prostaglandin G/H synthase-l? (PGHS-2) mRNA, quantitated by reverse transcription-polym erase chain reaction (RT-PCR). The mRNA induction for the constitutive isozyme PGHS-1 was less than that for PGHS-2. The interleukin-6 (IL-6 ) mRNA was also increased (6.4- to 9.3-fold) in microgravity as compar ed to the ground controls. Since PGE2. and IL-6 are both known to play a role in osteoclast formation and bone resorption, these data provid e molecular mechanisms that contribute to our understanding of microgr avity-induced alterations in the bone resorption process.