Investigating the role of PDGF as a potential drug therapy in bone formation and fracture healing

Graham, Simon Matthew; Leonidou, Andreas; Lester, Marie; Heliotis, Manolis; Mantalaris, Athanasios; Tsiridis, Eleftherios

doi:10.1517/13543780903241607

Cited by 92 publications

(60 citation statements)

References 70 publications

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“…9 Members of this family are disulfide-bonded polypeptides that have multifunctional roles ranging from embryonic development to wound healing. [10][11][12] PDGF signaling has been implicated in several pathologic disease states 9,[13][14][15][16][17] ; however, its role in HAND, specifically as it pertains to drug abuse-related changes in barrier permeability, has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability

Yao

Duan

Buch

2011

Blood

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Neuroinflammation associated with advanced HIV-1 infection is often exacerbated in cocaine-abusing, HIV-infected patients. The underlying mechanisms could, in part, be attributed to the increased impairment of blood brain barrier integrity in the presence of cocaine. Plateletderived growth factor (PDGF) has been implicated in several pathologic conditions, specifically attributable to its potent mitogenic effects. Its modulation by drug abuse, however, has received very little attention. In the present study, we demonstrated cocaine-mediated induction of PDGF-BB in human brain microvascular endothelial cells through the binding to its cognate receptor. Furthermore, this effect was mediated, with subsequent activation of mitogen-activated protein kinases and Egr-1 pathways, culminating ultimately into increased expression of PDGF-BB. Cocaine exposure resulted in increased permeability of the endothelial barrier, and this effect was abrogated in mice exposed to PDGF-BB neutralizing antibody, thus underscoring its role as a vascular permeant. In vivo relevance of these findings was further corroborated in cocaine-treated mice that were administered neutralizing antibody specific for PDGF-BB as well as in Egr IntroductionAlthough the advent of combined antiretroviral therapy has significantly decreased the incidence of HIV-associated neurocognitive disorders (HANDs), the prevalence of the disease is actually increasing. Drug abuse has been implicated as a contributing risk factor for increased neuroinflammation associated with HIV-1 infection. Intriguingly, cocaine has been shown to open up the blood-brain barrier (BBB). 1-3 BBB is critical for the maintenance of central nervous system (CNS) homeostasis and for the regulation of the neuronal microenvironment. However, under conditions of barrier disruption as in HIV-1 infection, virus can enter the CNS through infected leukocytes likely via the Trojan horse mechanism.Zhang et al 3 have demonstrated that cocaine-mediated effects on the BBB are complex, including both direct proapoptotic effects on the endothelial cells as well as indirect paracrine effects that are manifested by proinflammatory modulators such as chemokines and cytokines. Cocaine plays a critical role in HIV-1 neuroinvasion, thus accelerating the progression of HAND. [1][2][3] Because the chemokine/growth factor platelet-derived growth factor (PDGF) has been shown in previous reports to be upregulated in the areas around the blood vessels in the brains of macaques with simian immunodeficiency virus infection, 4 we hypothesized that cocaine-mediated disruption of the endothelial barrier could involve PDGF. Adding further validity to this hypothesis was a recent report by Su et al 5 suggesting the role of a novel mediator of the PDGF family as a cerebrovascular permeant in ischemic stroke. Other investigators have also demonstrated the effects of PDGF on endothelial cells. [6][7][8] PDGF comprises a family of proteins that are the products of 4 genes (A-D) that are highly conserved throughout the anim...

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Section: Introductionmentioning

confidence: 99%

Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability

Yao

Duan

Buch

2011

Blood

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Hutton

Moore

Gimble

et al. 2013

Tissue Engineering Part A

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“…It has been also reported that during the early stages of wound healing PRP has a strong stimulant effect on capillary regeneration [33]. Particularly, the publications, which point out positive features of PRP over the last years, have stressed: factors (TGF-al and TGF32) for bone regeneration [51]. Our study used these principles for enhancing the osteoconductive property of a new highly purified bovine allograft (Laddec ® ) by addition of autologous PRP in regeneration of osseous defects of jaws caused by cystectomy.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Platelet-Rich-Plasma (PRP) and Highly Purified Bovine Xenograft (Laddec®) Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

S¹,

Guarnieri

2013

JOMR

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Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP) to a new highly purified bovine allograft (Laddec ® ) in the bone regeneration of cystic bony defects augmented following cystectomy. Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec ® . All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry surgery for implant placement, bone core was taken for histological and histomorphometric analysis. Results: The postoperative successive radiographs showed a good regeneration of bone in the height of bony defects with application of PRP to bone graft. By the first postoperative month, about 48% of the defect was filled, which gradually increased in each month and showed about 90% of defect-fill by 6 months. Histological and histomorphometric analysis, showed a significant presence of bone tissue and vessels, with newly formed bone in contact with anorganic bone particles. The mean volume of vital bone was 68 ± 1.6% and the mean percentage of vital bone was 48 ± 2.4%. The mean percentage of inorganic particles in tissues was 20 ± 1.2% of the total volume. All the samples analyzed did not evidence the presence of inflammatory cells. Conclusions:The results of this study showed how the use of Laddec ® in association with platelet-rich plasma allows bone regeneration and has a potential for routine clinical use for regeneration of cystic bony defects.

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Investigating the role of PDGF as a potential drug therapy in bone formation and fracture healing

Cited by 92 publications

References 70 publications

Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability

Cocaine-mediated induction of platelet-derived growth factor: implication for increased vascular permeability

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

Efficacy of Platelet-Rich-Plasma (PRP) and Highly Purified Bovine Xenograft (Laddec®) Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

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