DOWN-REGULATION OF TENASCIN EXPRESSION BY GLUCOCORTICOIDS IN BONE-MARROW STROMAL CELLS AND IN FIBROBLASTS

Tenascin, a predominantly mesenchymal extracellular matrix (ECM) glyco protein has a rather restricted tissue distribution, but until now fac tors that inhibit its expression have not been identified. Glucocortic oids are known to be beneficial for establishment of myelopoiesis in l ong-term bone marrow cultures. Tenascin was found to be expressed in t he bone marrow, and glucocorticoids were found to affect bone marrow t enascin expression. Both tenascin mRNAs and the mRNA of another ECM pr otein, laminin B1 chain, were drastically downregulated by glucocortic oids during initiation of bone marrow cultures. However, in already es tablished long-term cultures glucocorticoids did not affect laminin B1 chain mRNA levels although tenascin mRNAs continued to be downregulat ed. Studies with a stromal cell line (MC3T3-G2/PA6) and fibroblasts (3 T3) suggested that glucocorticoids act directly on the stromal cells t hat produce tenascin. In 3T3 cells this downregulation occurred within 12 h of glucocorticoid-treatment, suggesting that glucocorticoids act ed through cis regulatory elements of the tenascin gene. We suggest th at glucocorticoids in part regulate hematopoiesis by modifying the ECM . Furthermore, downregulation of tenascin expression by glucocorticoid s may in part explain the restricted tissue distribution of tenascin i n other tissues.