Receptor binding of PDGF‐AA and PDGF‐BB, and the modulation of PDGF receptors by TGF‐β, in human periodontal ligament cells

Abstract

The growth factors PDGF-AA and PDGF-BB have previously been shown to be potent mitogens for human periodontal ligament (hPDL) cells in vitro. Additionally, the mitogenic response to PDGF-AA has been shown to be specifically inhibited by TGF-beta. The purpose of the present investigation was to examine the binding of PDGF-AA and PDGF-BB, and the modulation of PDGF binding by TGF-beta, in hPDL cells. Scatchard analysis identified an average of 32,000 PDGF-AA high-affinity binding sites per cell with a dissociation constant (Kd) of 0.66 nM and an average of 36,000 PDGF-BB binding sites per cell with a dissociation constant (kd) of 0.44 nM. After treatment with TGF-beta, the receptor number for PDGF-AA was found to specifically decrease by approximately 50%, with no change in binding affinity. This reduced number of binding sites was shown to correlate with both a decrease in levels of receptor tyrosine phosphorylation and a decreased number of alpha receptor subunits. Northern blot analysis identified the TGF-beta-mediated decrease in PDGF alpha receptor subunit mRNA levels. PDGF-BB showed little change in the number of binding sites or in the binding affinity with TGF-beta treatment, and the data were consistent with an increase in the number of beta receptor subunits. These results demonstrate nearly equivalent numbers of receptors for both PDGF-AA and PDGF-BB in hPDL cells. Also, modulation of PDGF binding, by TGF-beta, was shown to result in a reduced number of alpha receptor subunits with an increase in the number of beta receptor subunits.

PDGF-α Receptor Subunit Expression Down-regulated by IL-1β in Human Periodontal Ligament Cells

“…Previous investigations have shown PDL cells to have predominantly PDGF-ot receptor subunits on the cell surface (Oates et al, 1995). It is our working hypothesis that there are endogenous factors within the periodontal wound that down-regulate the PDGF receptors in PDL cells, and ultimately limit the regenerative response to PDGF.…”

“…The relative abundance of the two receptor subunits has been shown to be a critical factor in the cellular response to a specific PDGF isoform (Heldin et al, 1988;Seifert et al, 1989). In addition, it has been shown that the expression of these receptors may be influenced by other growth factors and cytokines (Gilardetti et al, 1991;Oates et al, 1995). Therefore, an understanding of the modulating influences J Dent Res 77(10) 1998 of endogenous cytokines and growth factors present in a periodontal wound may be important in optimizing the regenerative potential of PDGF.…”

“…Similar down-regulation of PDGF receptors in PDL cells may functionally limit their responsiveness to both endogenous and exogenous growth factors. We have previously demonstrated that human PDL cells have predominantly PDGF-ot receptor subunits, and the expression of these receptor subunits is down-regulated by the locally acting molecule, transforming growth factor-beta (TGF-3;Oates et al, 1995). Since TGF-3 is released from platelets and macrophages in response to wounding, and from osseous tissue during the resorptive process, it is likely that TGF-I is present in significant amounts in the periodontal wound site.…”

Improving Gingival Aesthetics Using Platelet Rich Fibrin and Synthetic Collagen Membrane: A Report of Two Cases

“…Platelet rich fibrin acts as a source of growth factors. Oates et al, have studied that growth factors (PDGF)-AA and PDGF-BB were major mitogens for human periodontal ligament cells, and transforming growth factor (TGF)-1 played a role as a regulator of the mitogenic responses [13]. Kawase et al, have proposed that platelet rich fibrin clot stimulates the formation of type 1 collagen in periodontal ligaments and osteoblastic cells invitro [12].…”

“…In vitro studies have demonstrated that the use of platelet rich fibrin helps is the better and faster healing of the operative site [11][12][13]. Platelet rich fibrin acts as a source of growth factors.…”