1α,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 identified polypeptide that stimulates growth of fibroblasts and enhances neurite 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: 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) for 24 h. However, PTN mRNA 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 dose-dependent manner in a dose range between 10(-11) M: to 10(-8) M: . This effect was specific to 1,25(OH)(2)D(3), since PTN mRNA levels were not affected by other steroids such as retinoic acid and dexamethasone in 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-enriched fetal rat calvaria cells as well as cultures of MC3T3-E1 and ROS17/2.8 cells. These observations suggest that PTN expression in osteoblasts is regulated by the calcitropic hormone, 1,25(OH)(2)D(3), and that PTN may play a role in vitamin D-dependent regulation of bone metabolism.