Editing Platelet-derived growth factor (section)

== Function ==
PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated [[mesenchyme]] and some [[progenitor]] populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal.<ref>{{cite journal|last1=Ataliotis|first1=P|last2=Symes|first2=K|last3=Chou|first3=MM|last4=Ho|first4=L|last5=Mercola|first5=M|title=PDGF signalling is required for gastrulation of Xenopus laevis.|journal=Development|date=September 1995|volume=121|issue=9|pages=3099–3110|doi=10.1242/dev.121.9.3099|pmid=7555734}}</ref><ref>{{cite journal|last1=Symes|first1=K|last2=Mercola|first2=M|title=Embryonic mesoderm cells spread in response to platelet-derived growth factor and signaling by phosphatidylinositol 3-kinase.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=3 September 1996|volume=93|issue=18|pages=9641–4|pmid=8790383|doi=10.1073/pnas.93.18.9641|pmc=38481|bibcode=1996PNAS...93.9641S|doi-access=free}}</ref><ref name="PUB00014075">{{cite journal |vauthors=Hoch RV, Soriano P | title = Roles of PDGF in animal development | journal = Development | volume = 130 | issue = 20 | pages = 4769–4784 | year = 2003 | pmid = 12952899 | doi = 10.1242/dev.00721 | s2cid = 24124211 | doi-access =  }}</ref> Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C)<ref name="PUB00004886">{{cite journal |vauthors=Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U | title = Vascular endothelial growth factor B, a novel growth factor for endothelial cells | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 6 | pages = 2567–2581 | year = 1996 | pmid = 8637916 | pmc = 39839 | doi = 10.1073/pnas.93.6.2576 | bibcode = 1996PNAS...93.2576O | doi-access = free }}</ref><ref name="PUB00001288">{{cite journal |vauthors=Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K | title = A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases | journal = EMBO J. | volume = 15 | issue = 2 | pages = 290–298 | year = 1996 | pmid = 8617204 | pmc = 449944 | doi = 10.1002/j.1460-2075.1996.tb00359.x }}</ref> which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.<ref name="PUB00004494">{{cite journal |vauthors=Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG | title = Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14 | journal = Oncogene | volume = 8 | issue = 4 | pages = 925–931 | year = 1993 | pmid = 7681160 }}</ref>

PDGF plays a role in [[embryo]]nic development, cell proliferation, cell migration, and [[angiogenesis]].<ref>{{cite web |url=http://www.multi-targetedtherapy.com/pdgfSignaling.asp |title=PDGF Pathways |access-date=2007-11-17 |url-status=dead |archive-url=https://web.archive.org/web/20061113131941/http://www.multi-targetedtherapy.com/pdgfSignaling.asp |archive-date=2006-11-13 }}</ref> Over-expression of PDGF has been linked to several [[disease]]s such as [[atherosclerosis]], fibrotic disorders and malignancies.  Synthesis occurs due to external stimuli such as thrombin, low oxygen tension, or other cytokines and growth factors.<ref name="pmid16970222">{{cite journal |vauthors=Alvarez RH, Kantarjian HM, Cortes JE | title = Biology of platelet-derived growth factor and its involvement in disease | journal = Mayo Clin. Proc. | volume = 81 | issue = 9 | pages = 1241–1257 | date = September 2006 | pmid = 16970222 | doi = 10.4065/81.9.1241 }}</ref>

PDGF is a required element in cellular division for [[fibroblasts]], a type of connective tissue cell that is especially prevalent in wound healing.<ref name="pmid16970222"/> In essence, the PDGFs allow a cell to skip the [[cell cycle|G1 checkpoints]] in order to divide.<ref name="pmid15784165">{{cite journal |vauthors=Song G, Ouyang G, Bao S | title = The activation of Akt/PKB signaling pathway and cell survival | journal = J. Cell. Mol. Med. | volume = 9 | issue = 1 | pages = 59–71 | year = 2005 | pmid = 15784165 | doi = 10.1111/j.1582-4934.2005.tb00337.x | pmc = 6741304 }}</ref> It has been shown that in monocytes-macrophages and fibroblasts, exogenously administered PDGF stimulates chemotaxis, proliferation, and gene expression and significantly augmented the influx of inflammatory cells and fibroblasts, accelerating extracellular matrix and collagen formation and thus reducing the time for the healing process to occur.<ref name="pmid2045423">{{cite journal |vauthors=Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A | title = Role of platelet-derived growth factor in wound healing | journal = J. Cell. Biochem. | volume = 45 | issue = 4 | pages = 319–326 | date = April 1991 | pmid = 2045423 | doi = 10.1002/jcb.240450403 | s2cid = 8539542 }}</ref>

In terms of osteogenic differentiation of mesenchymal stem cells, comparing PDGF to epidermal growth factor (EGF), which is also implicated in stimulating cell growth, proliferation, and differentiation,<ref name="Kratchmarova, I 2005" /> MSCs were shown to have stronger osteogenic differentiation into bone-forming cells when stimulated by epidermal growth factor (EGF) versus PDGF.  However, comparing the signaling pathways between them reveals that the PI3K pathway is exclusively activated by PDGF, with EGF having no effect. Chemically inhibiting the PI3K pathway in PDGF-stimulated cells negates the differential effect between the two growth factors, and actually gives PDGF an edge in osteogenic differentiation.<ref name="Kratchmarova, I 2005">{{cite journal |vauthors=Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M | title = Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation | journal = Science | volume = 308 | issue = 5727 | pages = 1472–1477 | date = June 2005 | pmid = 15933201 | doi = 10.1126/science.1107627 | bibcode = 2005Sci...308.1472K | s2cid = 10690497 }}</ref> [[Wortmannin]] is a PI3K-specific inhibitor, and treatment of cells with Wortmannin in combination with PDGF resulted in enhanced osteoblast differentiation compared to just PDGF alone, as well as compared to EGF.<ref name="Kratchmarova, I 2005"/> These results indicate that the addition of Wortmannin can significantly increase the response of cells into an osteogenic lineage in the presence of PDGF, and thus might reduce the need for higher concentrations of PDGF or other growth factors, making PDGF a more viable growth factor for osteogenic differentiation than other, more expensive growth factors currently used in the field such as BMP2.<ref>Hayashi, A. The New Standard of Care for Nonunions?.  AAOS Now. 2009.</ref>

PDGF is also known to maintain proliferation of [[oligodendrocyte progenitor cell]]s (OPCs).<ref>{{cite journal |vauthors=[[Ben Barres|Barres BA]], Hart IK, Coles HS, Burne JF, Voyvodic JT, Richardson WD, Raff MC | title = Cell Death and Control of Cell Survival in the Oligodendrocyte Lineage | journal = Cell | volume = 70 | issue = 1 | pages = 31–46 | year = 1992 | pmid = 1623522 | doi = 10.1016/0092-8674(92)90531-G | s2cid = 11529297 }}</ref><ref name="ReferenceA">{{MeshName|Proto-Oncogene+Proteins+c-sis}}</ref> It has also been shown that fibroblast growth factor (FGF) activates a signaling pathway that positively regulates the PDGF receptors in OPCs.<ref name="pmid2171589">{{cite journal |vauthors=McKinnon RD, Matsui T, Dubois-Dalcq M, Aaronson SA | title = FGF modulates the PDGF-driven pathway of oligodendrocyte development | journal = Neuron | volume = 5 | issue = 5 | pages = 603–614 | date = November 1990 | pmid = 2171589 | doi = 10.1016/0896-6273(90)90215-2 | s2cid = 23026544 }}</ref>