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Medicina (Kaunas, Lithuania) Mar 2023Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of... (Review)
Review
Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of periodontal regeneration, both in research and clinical practice. Outcomes of histologic studies are particularly valuable when interpreted considering additional evidence available from pre-clinical and clinical studies. One of the best-documented growth factors areproven to have positive effects on a myriad of oral regenerative procedures is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). While a systematic review of clinical studies evaluating rhPDGF in oral regenerative procedures has been recently completed, a review article that focuses on the histologic outcomes is needed. Hence, this communication discusses the histologic effects of rhPDGF-BB on oral and periodontal regenerative procedures, including root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration. Studies from 1989 to 2022 have been included in this review.
Topics: Humans; Becaplermin; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Intercellular Signaling Peptides and Proteins; Furcation Defects
PubMed: 37109634
DOI: 10.3390/medicina59040676 -
European Cells & Materials Jul 2017To promote and support tendon healing, one viable strategy is the use or administration of growth factors at the wound/rupture site. Platelet derived growth factor-BB... (Review)
Review
To promote and support tendon healing, one viable strategy is the use or administration of growth factors at the wound/rupture site. Platelet derived growth factor-BB (PDGF-BB), together with other growth factors, is secreted by platelets after injury. PDGF-BB promotes mitogenesis and angiogenesis, which could accelerate tendon healing. Therefore, in vitro studies with PDGF-BB have been performed to determine its effect on tenocytes and tenoblasts. Moreover, accurate and sophisticated drug delivery devices, aiming for a sustained release of PDGF-BB, have been developed, either by using heparin-binding and fibrin-based matrices or different electrospinning techniques. In this review, the structure and composition, as well as the healing process of tendons, are described. Part A deals with in vitro studies. They focus on the multiple effects evoked by PDGF-BB on the cellular level. Moreover, they address strategies for the sustained delivery of PDGF-BB. Part B focuses on animal models used to test different delivery strategies for PDGF-BB, in the context of tendon reconstruction. These studies showed that dosage and timing of PDGF-BB application are the most important factors for deciding which delivery device should be applied for a specific tendon laceration.
Topics: Animals; Becaplermin; Drug Delivery Systems; Humans; Models, Biological; Proto-Oncogene Proteins c-sis; Signal Transduction; Tendons; Wound Healing
PubMed: 28714058
DOI: 10.22203/eCM.v034a02 -
Clinical Interventions in Aging 2008Diabetic foot ulcers remain a major cause of morbidity. Significant progress has been accomplished in ulcer healing by improved management of both ischemia and... (Review)
Review
Diabetic foot ulcers remain a major cause of morbidity. Significant progress has been accomplished in ulcer healing by improved management of both ischemia and neuropathy in the diabetic foot. Nevertheless, there is a vital need for further improvement. Becaplermin gel represents an important therapeutic advance for diabetic neuropathic foot ulcers with adequate blood supply. Randomized controlled trials have shown that it is effective in increasing healing rates. However, this efficacy has not translated to positive clinical experience, and the drug is not widely used. Moreover, becaplermin is an expensive medication. Even though it has repeatedly been estimated as cost-effective, its high cost may be prohibitive for some clinicians, especially in developing countries. Clearly, further work is needed to clarify whether use of becaplermin is justified in everyday clinical practice. Future research also needs to assess the potential room for improvement with becaplermin, for instance by combination with other growth factors or by exploring alternative modes of drug delivery.
Topics: Angiogenesis Inducing Agents; Becaplermin; Diabetic Foot; Gels; Humans; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Randomized Controlled Trials as Topic; Treatment Outcome; Wound Healing
PubMed: 18686746
DOI: 10.2147/cia.s1106 -
Sovremennye Tekhnologii V Meditsine 2021Platelet-derived growth factor (PDGF) plays an important role in angiogenesis, affects activation of migration and proliferation of mesenchymal stem cells, fibroblasts,...
UNLABELLED
Platelet-derived growth factor (PDGF) plays an important role in angiogenesis, affects activation of migration and proliferation of mesenchymal stem cells, fibroblasts, smooth muscle cells, osteoblasts; activation of migration of monocytes, macrophages, and neutrophils. was to study the effect of cryo-processing on the qualitative properties of platelet-rich autoplasma (PRP) at different time intervals.
MATERIALS AND METHODS
Autologous plasma preparations were obtained from the blood of 31 donors. The biological material was prepared by double centrifugation according to the protocol for obtaining P-PRP and L-PRP. Platelet count and the concentration of growth factors (PDGF-AA and PDGF-BB) were studied in fresh PRP preparations. In frozen PRP samples, the concentration of PDGF-AA and PDGF-BB was determined 2 weeks after cryo-processing and 2 months after cryo-processing at -35 °С. P-PRP and L-PRP samples activated with 10% CaCl solution and those non-activated were studied.
RESULTS
L-PRP preparations are significantly superior to P-PRP preparations: the concentration of platelets is 1.7 times higher in them. The level of PDGF-AA in non-activated L-PRP is 1.8 times higher than in non-activated P-PRP (p<0.05). The level of PDGF-AA is 1.5 times higher in activated L-PRP than in activated P-PRP (p<0.05). The level of PDGF-BB is 2.9 times higher in non-activated L-PRP than in non-activated P-PRP and 1.8 times higher in activated L-PRP than in activated P-PRP (p<0.05). The concentration of PDGF-BB in non-activated P-PRP sharply increases in the 2 week after freezing and remains at the same level after 2 months (p<0.05). The concentration of PDGF-BB in activated plasma does not change (p>0.05).
CONCLUSION
Cryo-processing of non-activated autologous L-PRP allows preserving and subsequently enhancing the properties of plasma concentrate, which makes it possible to apply it in clinical practice.
Topics: Becaplermin; Blood Platelets; Intercellular Signaling Peptides and Proteins; Platelet Count; Platelet-Rich Plasma
PubMed: 34796019
DOI: 10.17691/stm2020.12.6.07 -
Journal of Diabetes and Its... 2014The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular pathway interactions of these markers found to be consistently associated with DR. Relevant databases [PubMed and ISI web of science] were searched for all published articles investigating molecular biomarkers of the vitreous associated with DR. Based on set exclusion/inclusion criteria available data from studies with human vitreous samples were extracted and used for our meta-analysis. The interactions of significant biomarkers in DR were investigated via STRING and KEGG pathway analysis. Our meta-analysis of DR identifies eleven biomarkers as potential therapeutic candidates alternate to current anti-VEGF therapy. Four of these are deemed viable therapeutic targets for PDR; ET receptors (ET A and ET B), anti-PDGF-BB, blocking TGF-β using cell therapy and PEDF. The identification of supplementary or synergistic therapeutic candidates to anti VEGF in the treatment of DR may aid in the development of future treatment trials.
Topics: Becaplermin; Biomarkers; Diabetic Retinopathy; Humans; Proto-Oncogene Proteins c-sis; Receptor, Endothelin A; Receptor, Endothelin B; Transforming Growth Factor beta; Vitreous Body
PubMed: 24630762
DOI: 10.1016/j.jdiacomp.2013.09.010 -
Expert Opinion on Drug Delivery Sep 2006The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these... (Review)
Review
The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. Growth factors are critical to the development, maturation, maintenance and repair of craniofacial tissues, as they establish an extracellular environment that is conducive to cell and tissue growth. Tissue-engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. These materials have been constructed into devices that can be used as vehicles for delivery of cells, growth factors and DNA. In this review, different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral- and tooth-supporting structures, namely the periodontium and alveolar bone.
Topics: Animals; Becaplermin; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Drug Delivery Systems; Genetic Therapy; Growth Substances; Humans; Mouth Diseases; Periodontal Diseases; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Tissue Engineering; Transforming Growth Factor beta; Wound Healing
PubMed: 16948560
DOI: 10.1517/17425247.3.5.647 -
Hypertension (Dallas, Tex. : 1979) Apr 2023Vascular smooth muscle cells (SMCs) plasticity is a central mechanism in cardiovascular health and disease. We aimed at providing cellular phenotyping, epigenomic and...
BACKGROUND
Vascular smooth muscle cells (SMCs) plasticity is a central mechanism in cardiovascular health and disease. We aimed at providing cellular phenotyping, epigenomic and proteomic depiction of SMCs derived from induced pluripotent stem cells and evaluating their potential as cellular models in the context of complex diseases.
METHODS
Human induced pluripotent stem cell lines were differentiated using RepSox (R-SMCs) or PDGF-BB (platelet-derived growth factor-BB) and TGF-β (transforming growth factor beta; TP-SMCs), during a 24-day long protocol. RNA-Seq and assay for transposase accessible chromatin-Seq were performed at 6 time points of differentiation, and mass spectrometry was used to quantify proteins.
RESULTS
Both induced pluripotent stem cell differentiation protocols generated SMCs with positive expression of SMC markers. TP-SMCs exhibited greater proliferation capacity, migration and lower calcium release in response to contractile stimuli, compared with R-SMCs. Genes involved in the contractile function of arteries were highly expressed in R-SMCs compared with TP-SMCs or primary SMCs. R-SMCs and coronary artery transcriptomic profiles were highly similar, characterized by high expression of genes involved in blood pressure regulation and coronary artery disease. We identified and as key drivers of RepSox specific program. Extracellular matrix content contained more proteins involved in wound repair in TP-SMCs and higher secretion of basal membrane constituents in R-SMCs. Open chromatin regions of R-SMCs and TP-SMCs were significantly enriched for variants associated with blood pressure and coronary artery disease.
CONCLUSIONS
Both induced pluripotent stem cell-derived SMCs models present complementary cellular phenotypes of high relevance to SMC plasticity. These cellular models present high potential to study functional regulation at genetic risk loci of main arterial diseases.
Topics: Humans; Induced Pluripotent Stem Cells; Transcriptome; Proteomics; Coronary Artery Disease; Cell Differentiation; Becaplermin; Transforming Growth Factor beta; Cells, Cultured; Myocytes, Smooth Muscle; Chromatin
PubMed: 36655574
DOI: 10.1161/HYPERTENSIONAHA.122.19733 -
Molecular Medicine (Cambridge, Mass.) Feb 2024Pericytes are a vital component of the blood-brain barrier, and their involvement in acute inflammation was recently suggested. However, it remains unclear whether...
BACKGROUND
Pericytes are a vital component of the blood-brain barrier, and their involvement in acute inflammation was recently suggested. However, it remains unclear whether pericytes contribute to hypothalamic chronic inflammation and energy metabolism in obesity. The present study investigated the impact of pericytes on the pathophysiology of obesity by focusing on platelet-derived growth factor (PDGF) signaling, which regulates pericyte functions.
METHODS
Tamoxifen-inducible systemic conditional PDGF receptor β knockout mice (Pdgfrb-KO) and Calcium/calmodulin-dependent protein kinase type IIa (CaMKIIa)-positive neuron-specific PDGF receptor β knockout mice (Pdgfrb-KO) were fed a high-fat diet, and metabolic phenotypes before and 3 to 4 weeks after dietary loading were examined. Intracellular energy metabolism and relevant signal transduction in lipopolysaccharide- and/or platelet-derived growth factor-BB (PDGF-BB)-stimulated human brain pericytes (HBPCs) were assessed by the Seahorse XFe24 Analyzer and Western blotting. The pericyte secretome in conditioned medium from HBPCs was studied using cytokine array kit, and its impact on polarization was examined in bone marrow-derived macrophages (BMDMs), which are microglia-like cells.
RESULTS
Energy consumption increased and body weight gain decreased after high-fat diet loading in Pdgfrb-KO mice. Cellular oncogene fos (cFos) expression increased in proopiomelanocortin (POMC) neurons, whereas microglial numbers and inflammatory gene expression decreased in the hypothalamus of Pdgfrb-KO mice. No significant changes were observed in Pdgfrb-KO mice. In HBPCs, a co-stimulation with lipopolysaccharide and PDGF-BB shifted intracellular metabolism towards glycolysis, activated mitogen-activated protein kinase (MAPK), and modulated the secretome to the inflammatory phenotype. Consequently, the secretome showed an increase in various proinflammatory chemokines and growth factors including Epithelial-derived neutrophil-activating peptide 78 (C-X-C motif chemokine ligand (CXCL)5), Thymus and activation-regulated chemokine (C-C motif chemokine (CCL)17), Monocyte chemoattractant protein 1 (CCL2), and Growth-regulated oncogene α (CXCL1). Furthermore, conditioned medium from HBPCs stimulated the inflammatory priming of BMDMs, and this change was abolished by the C-X-C motif chemokine receptor (CXCR) inhibitor. Consistently, mRNA expression of CXCL5 was elevated by lipopolysaccharide and PDGF-BB treatment in HBPCs, and the expression was significantly lower in the hypothalamus of Pdgfrb-KO mice than in control Pdgfrb mice (FL) following 4 weeks of HFD feeding.
CONCLUSIONS
PDGF receptor β signaling in hypothalamic pericytes promotes polarization of macrophages by changing their secretome and contributes to the progression of obesity.
Topics: Mice; Humans; Animals; Platelet-Derived Growth Factor; Pericytes; Becaplermin; Receptor, Platelet-Derived Growth Factor beta; Culture Media, Conditioned; Lipopolysaccharides; Signal Transduction; Inflammation; Mice, Knockout; Obesity; Hypothalamus; Proto-Oncogene Proteins c-sis
PubMed: 38317079
DOI: 10.1186/s10020-024-00793-z -
Scientific Reports Feb 2022Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been...
Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been proposed as a promising factor for preventing tooth ankylosis. Using rat tooth replantation model, we investigated whether PDGF-BB accelerates the repair of PDL after tooth replantation without ankylosis, and its molecular mechanisms. In PDGF-BB pretreated replanted teeth (PDGF-BB group), ankylosis was markedly reduced and functionally organized PDL collagen fibers were restored; the mechanical strength of the healing PDL was restored to an average of 76% of that in non-replanted normal teeth at 21 days. The numbers of PDGF-Rβ- and BrdU-positive cells in the periodontal tissues of the PDGF-BB group were greater than those of atelocollagen pretreated replanted teeth (AC group). Moreover, in the PDGF-BB group, the periodontal tissues had fewer osteocalcin-positive cells and decreased number of nuclear β-catenin-positive cells compared to those in the AC group. In vitro analyses showed that PDGF-BB increased the proliferation and migration of human periodontal fibroblasts. PDGF-BB downregulated mRNA expressions of RUNX2 and ALP, and inhibited upregulatory effects of Wnt3a on β-catenin, AXIN2, RUNX2, COL1A1, and ALP mRNA expressions. These findings indicate that in tooth replantation, topical PDGF-BB treatment enhances cell proliferation and migration, and inhibits canonical Wnt signaling activation in bone-tooth ankylosis, leading to occlusal loading of the PDL tissues and subsequent functional restoration of the healing PDL. This suggests a possible clinical application of PDGF-BB to reduce ankylosis after tooth replantation and promote proper regeneration of PDL.
Topics: Animals; Ankylosis; Becaplermin; Core Binding Factor Alpha 1 Subunit; Periodontal Ligament; Proto-Oncogene Proteins c-sis; RNA, Messenger; Rats; Tooth Ankylosis; Tooth Replantation; beta Catenin
PubMed: 35217688
DOI: 10.1038/s41598-022-06865-6 -
International Journal of Molecular... Sep 2022The investigation of effective therapeutic drugs for pulmonary hypertension (PH) is critical. KIR2.1 plays crucial roles in regulating cell proliferation and migration,...
The investigation of effective therapeutic drugs for pulmonary hypertension (PH) is critical. KIR2.1 plays crucial roles in regulating cell proliferation and migration, and vascular remodeling. However, researchers have not yet clearly determined whether KIR2.1 participates in the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and its role in pulmonary vascular remodeling (PVR) also remains elusive. The present study aimed to examine whether KIR2.1 alters PASMC proliferation and migration, and participates in PVR, as well as to explore its mechanisms of action. For the experiment, a PH model was established by intraperitoneally injecting Sprague‑Dawley rats monocrotaline (MCT). Hematoxylin and eosin staining revealed evidence of PVR in the rats with PH. Immunofluorescence staining and western blot analysis revealed increased levels of the KIR2.1, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) proteins in pulmonary blood vessels and lung tissues following exposure to MCT, and the TGF‑β1/SMAD2/3 signaling pathway was activated. For the experiments, the KIR2.1 inhibitor, ML133, or the TGF‑β1/SMAD2/3 signaling pathway blocker, SB431542, were used to pre‑treat human PASMCs (HPASMCs) for 24 h, and the cells were then treated with platelet‑derived growth factor (PDGF)‑BB for 24 h. Scratch and Transwell assays revealed that PDGF‑BB promoted cell proliferation and migration. Immunofluorescence staining and western blot analysis demonstrated that PDGF‑BB upregulated OPN and PCNA expression, and activated the TGF‑β1/SMAD2/3 signaling pathway. ML133 reversed the proliferation and migration induced by PDGF‑BB, inhibited the expression of OPN and PCNA, inhibited the TGF‑β1/SMAD2/3 signaling pathway, and reduced the proliferation and migration of HPASMCs. SB431542 pre‑treatment also reduced cell proliferation and migration; however, it did not affect KIR2.1 expression. On the whole, the results of the present study demonstrate that KIR2.1 regulates the TGF‑β1/SMAD2/3 signaling pathway and the expression of OPN and PCNA proteins, thereby regulating the proliferation and migration of PASMCs and participating in PVR.
Topics: Animals; Becaplermin; Cell Proliferation; Humans; Hypertension, Pulmonary; Monocrotaline; Myocytes, Smooth Muscle; Proliferating Cell Nuclear Antigen; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1; Vascular Remodeling
PubMed: 35856410
DOI: 10.3892/ijmm.2022.5175