SPACEFLIGHT HAS COMPARTMENT-SPECIFIC AND GENE-SPECIFIC EFFECTS ON MESSENGER-RNA LEVELS FOR BONE-MATRIX PROTEINS IN RAT FEMUR

In the present study, we evaluated the possibility that the abnormal b one matrix produced during spaceflight may be associated with reduced expression of bone matrix protein genes. To test this possibility, we investigated the effects of a 14-day spaceflight (SLS-2 experiment) on steady-state mRNA levels for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), osteocalcin, osteonectin, and prepro-alpha(1) subunit of typ e I collagen in the major bone compartments of rat femur. There were p ronounced site-specific differences in the steady-state levels of expr ession of the mRNAs for the three bone matrix proteins and GAPDH in no rmal weight-bearing rats, and these relationships were altered after s paceflight. Specifically, spaceflight resulted in decreases in mRNA le vels for GAPDH (decreased in proximal metaphysis), osteocalcin (decrea sed in proximal metaphysis), osteonectin (decreased in proximal and di stal metaphysis), and collagen (decreased in proximal and distal metap hysis) compared with ground controls. There were no changes in mRNA le vels for matrix proteins or GAPDH in the shaft and distal epiphysis. T hese results demonstrate that spaceflight leads to site- and gene-spec ific decreases in mRNA levels for bone matrix proteins. These findings are consistent with the hypothesis that spaceflight-induced decreases in bone formation are caused by concomitant decreases in expression o f genes for bone matrix proteins.