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 (PTX), a nonspecific inhibitor of phosphodiesterases (PDEs), that causes elevation of the intracellular cyclic adenosine monophosphate (cAMP) level on the BMP-4-induced chondro/osteogenic differentiation of a mesenchymal cell line, C3H10T1/2; a bone marrow stromal cell line, ST2; and an osteoblastic cell line, 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.
Tsutsumimoto
T
T
Department of Orthopaedic Surgery, Shinshu University School of Medicine, Nagano, Japan. tsutsu@plum.ocn.ne.jp
Wakabayashi
S
S
Kinoshita
T
T
Horiuchi
H
H
Takaoka
K
K
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D010431:Pentoxifylline