Platelet-Derived Growth Factor Receptor Signaling Is Not Involved in Osteogenic Differentiation of Human Mesenchymal Stem Cells

Abstract

Platelet-derived growth factor (PDGF) receptor signaling plays an important role in the regulation of proliferation and migration of skeletal cells such as osteoblasts or mesenchymal stem cells (MSCs). However, involvement of these receptors in the process of osteoblastic differentiation of MSCs is still a matter of debate. The aim of our study was to examine the role of PDGF receptor signaling in osteogenic differentiation of human MSCs. For this purpose, we performed PDGF receptor stimulation as well as inhibition experiments. Inhibition experiments were carried out with Tyrphostin AG1296, a potent and specific inhibitor of PDGF receptor activity. As expected, Tyrphostin AG1296 treatment caused a concentration-dependent decrease in fetal calf serum and PDGF-BB-induced proliferation of MSCs and effectively inhibited PDGF-BB-induced phosphorylation of extracellular-regulated kinase 1/2. However, PDGF receptor inhibition had no significant effect on osteoblastic differentiation of MSCs, as evaluated histochemically by von Kossa, Alizarin-Red, and osteocalcin stainings. Moreover, mineralized matrix production, as assayed by quantitative Ca(2+)-measurements, was also not modulated by Tyrphostin AG1296 treatment. These results were noticeable irrespective of whether MSCs were grown under nonosteogenic or osteogenic differentiation conditions. Similarly, PDGF-BB treatment of MSCs in receptor stimulation experiments also failed to modulate mineralization. However, expression of alkaline phosphatase was suppressed by Tyrphostin AG1296 treatment at later stages of osteogenesis but not in the early stages, as assessed by enzyme activity and mRNA expression assays. Expression of other osteogenic marker genes such as osteocalcin, runt-related transcription factor 2, osteopontin, collagen type I, and bone sialoprotein was almost unaffected in our perturbation studies. From these experiments, we conclude that PDGF receptor signaling sustains proliferation without affecting osteogenic differentiation of MSCs.

Human multipotent mesenchymal stem cells improve healing after collagenase tendon injury in the rat

“…A similar effect on osteodifferentiation was previously described by Chevallier, Parsons and Prinse [17-19]; this effect can be related to the age of the platelet donors [20]. Other authors have cast doubts on the influence of platelet lysate on osteogenic differentiation [21-23]. Further experiments in this area are needed in order to utilize expanded hMSCs in therapeutic protocols for tendon healing because osteogenesis in tendons is undesirable and must be prevented.…”

Platelet-Derived Growth Factor and Spatiotemporal Cues Induce Development of Vascularized Bone Tissue by Adipose-Derived Stem Cells

“…This response may be somewhat unique to ASCs, as previous studies have shown that PDGF signaling either has no effect or even an inhibitory effect on the osteogenic differentiation of bone marrowderived MSCs. [33][34][35][36][37] In vascular cultures, PDGF signaling had minimal effects on vascular network properties, with only low levels of exogenous PDGF-BB contributing to a slight increase in network density. PDGF signaling did, however, significantly affect pericyte coverage of the vessels.…”

“…[27][28][29] A number of studies have demonstrated that in vivo administration of exogenous PDGF-BB significantly enhances bone formation. [30][31][32] Yet, in vitro studies with MSCs have reported that while exogenous PDGF-BB induces greater proliferation, it has no effect on, [33][34][35] or may even be inhibitory to, 36,37 osteogenic differentiation. With regard to ASCs, it has been shown that during osteogenic differentiation, their expression of the PDGF receptor b (PDGFR-b) is upregulated.…”

Bone Formation Deregulations Are the Oncogenesis Keys in Osteosarcomas

“…I t i s a l s o promoting malignant cell motility (Kumar et al, 2010) and it is implicated in osteoblastosteoclast interactions (Sanchez-Fernandez et al, 2008). When the PDGF/PDGFR signaling pathway is stimulated, the patients are presenting a worst prognosis (Hassan et al, 2011;Entz-Werlé et al, 2007b).…”