A phosphodiesterase inhibitor, pentoxifylline, enhances the bone morphogenetic protein-4 (BMP-4)-dependent differentiation of osteoprogenitor cells

Bone morphogenetic protein-4 (BMP-4), a member of the transforming growth factor-beta superfamily is capable of initiating differentiation of uncommitted mesenchymal cells into a chondro/osteogenic pathway. This Study reports the effects of pentoxifylline (PT-X), a nonspecific inhibitor of phosphodiesterases (PDEs), that causes elevation of the intracellular cyclic adenosine monophosphate (cAMP) level on the BMP4-induced chondro/osteogenic diffierentiation of a mesenchymal cell line. C3H10T1/2; a bone marrow stromal cell line ST2; and an osteoblastic cell fine, MC3T3-E1. It was found that PTX enhanced BMP-4-induced chondro/osteogenic differentiation in C3H10T1/2 and ST2 cells. Similar effects were observed when adding dibutyryl-cAMP and forskolin. These results indicate that cAMP may potentiate the action of BMP-4 on osteoprogenitor cells, highlighting, the possibility that PDE inhibitors could be used as therapeutic agents to enhance bone formation through this effect. (C) 2002 by Elsevier Science Inc. All rights reserved.