RAT TAIL SUSPENSION REDUCES MESSENGER-RNA LEVEL FOR GROWTH-FACTORS AND OSTEOPONTIN AND DECREASES THE OSTEOBLASTIC DIFFERENTIATION OF BONE-MARROW STROMAL CELLS

We previously reported that bone marrow stromal cells produce insulin- like growth factors (IGF-I and -II), and that medium conditioned by ma rrow stromal cells stimulates osteoblast proliferation in vitro. The p resent study employed the rat tail-suspension model to unload the hind limbs. It was designed to test the hypothesis that the development of osteopenia or osteoporosis could be due to a deficit in the osteogenic function of marrow stromal cells, Although tail suspension suppressed body weight during the first 3 days of an Ii-day pair-fed study, the overall weight gain recorded by these animals was normal. Nevertheless , bone growth was inhibited by suspension, Similarly, the total adhere nt marrow stromal cell population harvested from the femurs and tibias was decreased by tail suspension, and only half the normal number of fibroblastic stromal cell colonies grew when they were cultured, The p roliferation of alkaline-phosphatase-positive cells in the stroma was also inhibited, Northern hybridization revealed that the messenger RNA level for transforming growth factor-beta(2) and IGF-II in stromal ce ll was reduced by tail suspension, The production of IGF-II by marrow stromal cells was also decreased, The steady-state level of five diffe rent transcript sizes of IGF-I mRNA was altered differentially by tail suspension, Osteopontin mRNA was also reduced in marrow stromal cells from tail-suspended rats compared with the normal rats, These data su ggest that skeletal unloading not only alters the mRNA level for growt h factors and peptide production, but also affects the proliferation a nd osteogenic differentiation of marrow stromal cells, These changes m ay be responsible for the reduced bone formation in osteopenia and ost eoporosis.