Transforming growth factor (TGF beta) decreases the proliferation of human bone marrow fibroblasts by inhibiting the platelet-derived growth factor (PDGF) binding.
Human bone marrow fibroblasts were cultivated and characterized by immunofluorescent staining and electron microscopy. Their interactions with PDGF and TGF beta were studied. While a positive intracellular antifibronectin staining was observed, the cultured cells were not labeled with specific antibodies toward factor VIII von Willebrand factor (F VIII/vWF), desmin, and macrophage antigen. Moreover, electron microscopy excluded the presence of endothelial cells by the absence of Weibel-Palade bodies. The binding of pure human PDGF to the cultured bone marrow fibroblasts was investigated. Addition of an excess of unlabeled PDGF decreased the binding to 75 and 80%, which means that the nonspecific binding represented 20-25% of total binding, whereas epidermal growth factor (EGF) had no effect. Two classes of sites were detected by Scatchard analysis with respectively 21,000 and 37,000 sites per cell, with a KD of 0.3 x 10(-10) M and KD of 0.5 x 10(-9) M. The stimulation of DNA synthesis by PDGF was quantified by [3H]thymidine incorporation. When PDGF was added alone at a concentration of 15 ng/ml, it induced a maximal DNA synthesis of 400%, which increased up to 900%, in the presence of platelet-poor plasma (PPP). On the other hand, PDGF-induced fibroblast proliferation was inhibited in a dose-dependent manner by TGF beta. This inhibition was related to a significantly decreased binding of 125I-labeled PDGF observed in the presence of TGF beta. Our results suggested that PDGF and TGF beta could modulate the growth of bone marrow fibroblasts.
Bryckaert
M C
MC
Hôpital Lariboisière, INSERM U150-CNRS UA 334, Paris, France.
Lindroth
M
M
Lönn
A
A
Tobelem
G
G
Wasteson
A
A
D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication; D005455:Fluorescent Antibody Technique; D006801:Humans; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D015291:Transforming Growth Factors / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D015291:Transforming Growth Factors