Platelet-derived growth factor
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Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood vessel tissue, mitogenesis, i.e. proliferation, of mesenchymal cells such as fibroblasts, osteoblasts, tenocytes, vascular smooth muscle cells and mesenchymal stem cells as well as chemotaxis, the directed migration, of mesenchymal cells. Platelet-derived growth factor is a dimeric glycoprotein that can be composed of two A subunits (PDGF-AA), two B subunits (PDGF-BB), or one of each (PDGF-AB).
PDGF
Though PDGF is synthesized,
Recombinant PDGF is used in medicine to help heal chronic ulcers and in orthopedic surgery and periodontics as an alternative to bone autograft to stimulate bone regeneration and repair.
Types and classification
There are five different
Mechanisms
The
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.[13][14][15] Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C)[16][17] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.[18]
PDGF plays a role in embryonic development, cell proliferation, cell migration, and angiogenesis.[19] Over-expression of PDGF has been linked to several diseases 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.[20]
PDGF is a required element in cellular division for
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,[23] 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.[23] 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.[23] 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.[24]
PDGF is also known to maintain proliferation of oligodendrocyte progenitor cells (OPCs).[25][26] It has also been shown that fibroblast growth factor (FGF) activates a signaling pathway that positively regulates the PDGF receptors in OPCs.[27]
History
PDGF was one of the first
Medicine
Recombinant PDGF is used to help heal chronic ulcers and in orthopedic surgery and periodontics to stimulate bone regeneration and repair.[30] PDGF may be beneficial when used by itself or especially in combination with other growth factors to stimulate soft and hard tissue healing (Lynch et al. 1987, 1989, 1991, 1995).
Research
Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for receptor antagonists to treat disease. Such antagonists include (but are not limited to) specific antibodies that target the molecule of interest, which act only in a neutralizing manner.[31]
The "c-Sis" oncogene is derived from PDGF.[26][32]
Age related downregulation of the PDGF receptor on islet beta cells has been demonstrated to prevent islet beta cell proliferation in both animal and human cells and its re-expression triggered beta cell proliferation and corrected glucose regulation via insulin secretion.[33][34]
A non-viral PDGF "bio patch" can regenerate missing or damaged bone by delivering DNA in a nano-sized particle directly into cells via genes. Repairing bone fractures, fixing craniofacial defects and improving dental implants are among potential uses. The patch employs a collagen platform seeded with particles containing the genes needed for producing bone. In experiments, new bone fully covered skull wounds in test animals and stimulated growth in human bone marrow stromal cells.[35][36]
The addition of PDGF at specific time‐points has been shown to stabilise vasculature in collagen‐glycosaminoglycan scaffolds.[37]
Family members
Human genes encoding proteins that belong to the platelet-derived growth factor family include:
See also
- Platelet-activating factor
- Platelet-derived growth factor receptor
- atheroma platelet involvement in smooth muscle proliferation
- Withaferin A potent inhibitor of angiogenesis
References
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- ^ Minarcik, John. "Global Path Course: Video". Archived from the original on 2018-09-29. Retrieved 2011-06-27.
- ^ "The Basic Biology of Platelet Growth Factors". September 2004. Retrieved 2014-05-08.
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- ^ "PDGF Pathways". Archived from the original on 2006-11-13. Retrieved 2007-11-17.
- ^ PMID 16970222.
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- ^ S2CID 10690497.
- ^ Hayashi, A. The New Standard of Care for Nonunions?. AAOS Now. 2009.
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- ^ a b Proto-Oncogene+Proteins+c-sis at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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Demonstration of the safety and efficacy of rhPDGF-BB in the healing of chronic foot ulcers in diabetic patients and regeneration of alveolar (jaw) bone lost due to chronic infection from periodontal disease has resulted in two FDA-approved products based on this molecule
- PMID 9211881.
- S2CID 9958016.
- ^ "Researchers make older beta cells act young again". Eurekalert.org. 2011-10-12. Retrieved 2013-12-28.
- ^ "New Stanford molecular target for diabetes treatment discovered". Med.stanford.edu – Stanford University School of Medicine. 2011-10-12. Archived from the original on 2013-10-21. Retrieved 2013-12-28.
- PMID 24161167. Retrieved 2013-12-28.
- PMID 24161167.
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External links
- platelet-derived+growth+factor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)