IL-1 and transforming growth factor-beta inhibit platelet-derived growth factor-AA binding to osteoblastic cells by reducing platelet-derived growth factor-alpha receptor expression.
Platelet-derived growth factor (PDGF) is thought to play a significant role in bone repair and regeneration. We previously demonstrated that PDGF-AA-induced chemotaxis and proliferation can be modulated by IL-1. We now report that IL-1 and transforming growth factor-beta (TGF-beta) significantly decrease the number of PDGF-AA binding sites in both normal and tumor-derived human osteoblastic cells, whereas PDGF-BB binding is minimally affected. The affinity of PDGF-AA binding remains unchanged in the presence of IL-1, but is slightly reduced by TGF-beta as demonstrated by Scatchard analysis. We also showed that tyrosyl kinase phosphorylation after PDGF-AA binding is decreased in the presence of both IL-1 and TGF-beta. Northern blot analysis indicates that both IL-1 and TGF-beta decrease the expression of PDGF-alpha receptor mRNA. These results suggest that IL-1 and TGF-beta have the potential to regulate PDGF-AA-induced biologic activity in normal human osteoblastic cells and in human osteoblastic sarcoma cells by decreasing the levels of the PDGF-alpha receptor.
Department of Oral Biology, Boston University School of Graduate Dentistry, MA.
Y L
YL
Yeh
Y M
YM
Kang
M S
MS
Chaibi
J F
JF
Xie
D T
DT
Graves
D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor