1-ALPHA,25-DIHYDROXYVITAMIN D-3 DOWN-REGULATES PLEIOTROPHIN MESSENGER-RNA EXPRESSION IN OSTEOBLAST-LIKE CELLS

Pleiotrophin (PTN)[heparin-binding-growth-associated molecule (HB-GAM) , heparin-binding neurite-promoting factor (HBNF)] is a recently ident ified polypeptide that stimulates growth of fibroblasts and enhances n eurite extension. PTN is expressed in many tissues but relatively high level of expression has been observed in brain and bone. We examined hormonal regulation of PTN mRNA expression in several osteoblast-like cell lines including MC3T3-E1 and ROS17/2.8. The levels of PTN mRNA in these cells was significantly reduced by treatment with 10(-8) M 1 al pha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) for 24 h. However, PTN mR NA levels were increased when the non-osteoblastic cell line, ROS 25/1 , was treated with 1,25(OH)(2)D-3. These effects were observed in a do se-dependent manner in a dose range between 10(-11) M to 10(-8) M. Thi s effect was specific to 1,25(OH)(2)D-3, since PTN mRNA levels were no t affected by other steroids such as retinoic acid and dexamethasone i n MC3T3-E1 or ROS17/2.8 cells. Similar 1,25(OH)(2)D-3 down-regulation of PTN mRNA was also observed in primary cultures of osteoblast-enrich ed fetal rat calvaria cells as well as cultures of MC3T3-E1 and ROS17/ 2.8 cells. These observations suggest that PTN expression in osteoblas ts is regulated by the calcitropic hormone, 1,25(OH)(2)D-3, and that P TN may play a role in vitamin D-dependent regulation of bone metabolis m.