The Effects of Platelet-Derived Growth Factor-BB on Healing of the Rabbit Medial Collateral Ligament

1998 ◽  
Vol 26 (4) ◽  
pp. 549-554 ◽  
Author(s):  
Kevin A. Hildebrand ◽  
Savio L-Y. Woo ◽  
David W. Smith ◽  
Christina R. Allen ◽  
Masataka Deie ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Medial Collateral Ligament ◽  
Fibrin Sealant ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Individual Growth ◽  
Control Group ◽  
Collateral Ligament ◽  
Ligament Healing

We report a biologic approach to improve medial collateral ligament healing using growth factors normally expressed in healing tissue. Our previous in vitro work demonstrated that platelet-derived growth factor-BB and transforming growth factor- 1 promoted fibroblast proliferation and matrix synthesis, respectively. Therefore, these growth factors were used in vivo to determine whether they could improve medial collateral ligament healing, whether this effect was dose-dependent, and if combinations of growth factors could improve healing more than individual growth factors. Thirty-seven rabbits had various doses of growth factors applied to the ruptured right medial collateral ligaments using a fibrin sealant delivery vehicle. The five groups consisted of 1) two groups receiving two doses of platelet-derived growth factor-BB, 2) two groups receiving two doses of this growth factor plus transforming growth factor- 1, and 3) one group receiving fibrin sealant only. After sacrifice at 6 weeks, biomechanical and histologic evaluations of the healing ligament were performed. Femur-medial collateral ligament-tibia complexes of the knees given the higher dose of platelet-derived growth factor-BB had ultimate load, energy absorbed to failure, and ultimate elongation values that were 1.6, 2.4, and 1.6 times greater than the same complexes of the control group. Adding transforming growth factor- 1 did not lead to any further increases in the structural properties of the complex compared with treatment with platelet-derived growth factor-BB. These encouraging results suggest that use of platelet-derived growth factor-BB may improve the quality of the healing medial collateral ligament, and that it may also have a similar potential for promoting healing of other ligaments.

Cytokines and Growth Factors Involved in Peritoneal Fibrosis of Peritoneal Dialysis Patients

2005 ◽  
Vol 28 (2) ◽  
pp. 129-134 ◽  
Author(s):  
K.-H. Oh ◽  
P.J. Margetts
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Fibroblast Growth Factors ◽  
Tissue Growth ◽  
Platelet Derived Growth Factor ◽  
Fibroblast Growth ◽  
Dialysis Patients ◽  
Peritoneal Fibrosis

Peritoneal fibrosis is initiated by exposure of peritoneal tissues to numerous harmful agents encountered during peritoneal dialysis. These agents interact with cells within the peritoneum to induce growth factors and cytokines that are important in the initiation, progression and maintenance of fibrosis. Some of the mediators implicated in the pathogenesis of peritoneal fibrosis include transforming growth factor (TGF) ß, connective tissue growth factor (CTGF), fibroblast growth factors (FGF), and platelet derived growth factor (PDGF).

Effects of Administration of Exogenous Growth Factors on Biomechanical Properties of the Elongation-type Anterior Cruciate Ligament Injury with Partial Laceration

2005 ◽  
Vol 33 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Eiji Kondo ◽  
Kazunori Yasuda ◽  
Masanori Yamanaka ◽  
Akio Minami ◽  
Harukazu Tohyama
Keyword(s):  
Anterior Cruciate Ligament ◽  
Growth Factors ◽  
Growth Factor ◽  
Fibrin Sealant ◽  
Transforming Growth Factor ◽  
Cruciate Ligament ◽  
Transforming Growth Factor Β1 ◽  
Ligament Injury ◽  
Group 3 ◽  
Anterior Cruciate

Background No studies have been conducted to clarify the in vivo effect of growth factor application on healing in the injured anterior cruciate ligament. Hypothesis Administration of exogenous growth factors significantly increases the structural properties of the injured anterior cruciate ligament. Study Design Controlled laboratory study. Methods Thirty-six rabbits were randomly divided into 4 groups of 9 animals each after an overstretched injury was made in the right anterior cruciate ligament. In group 1, no treatment was applied around the injured anterior cruciate ligament. In group 2, 0.2 mL fibrin sealant was applied around it. In group 3, 4 ng transforming growth factor–β1 mixed with 0.2 mL fibrin sealant was applied. In group 4, 20 μg platelet-derived growth factor–BB mixed with 0.2 mL fibrin sealant was applied. Each rabbit was sacrificed at 12 weeks after the surgery. In addition, 9 knees randomly harvested from all the left knees were used to obtain normal control data. The femur–anterior cruciate ligament–tibia complex specimens were biomechanically and histologically evaluated. Results Concerning the maximum load and the stiffness, group 3 was significantly greater than groups 1 and 2, whereas there were no significant differences among groups 1, 2, and 4. Groups 1, 2, 3, and 4 were significantly lower than the control group. Conclusions The application of 4 ng transforming growth factor–β1 significantly enhances healing in the injured anterior cruciate ligament. Clinical Relevance Administration of certain growth factors is of value to be studied as one of the future therapeutic options for the overstretched anterior cruciate ligament injury.

scholarly journals Neuroblastoma cells express c-sis and produce a transforming growth factor antigenically related to the platelet-derived growth factor.

1985 ◽  
Vol 5 (9) ◽  
pp. 2289-2297 ◽  
Author(s):  
E J van Zoelen ◽  
W J van de Ven ◽  
H J Franssen ◽  
T M van Oostwaard ◽  
P T van der Saag ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Rat Kidney ◽  
Molecular Size ◽  
Platelet Derived Growth Factor ◽  
Kidney Cells ◽  
Transforming Growth Factors ◽  
Normal Rat ◽  
Epidermal Growth

Mouse neuroblastoma Neuro-2A cells produce transforming growth factors during exponential growth in a defined hormone-free medium, which, on Bio-Gel columns in 1 M HAc, elute at a molecular size of 15 to 20 kilodaltons (kDa). These neuroblastoma-derived transforming growth factors have strong mitogenic activity, but they do not compete with epidermal growth factor for receptor binding (E. J. J. van Zoelen, D. R. Twardzik, T. M. J. van Oostwaard, P. T. van der Saag, S. W. de Laat, and G. J. Todaro, Proc. Natl. Acad. Sci. U.S.A. 81:4085-4089, 1984). In this study approximately 80% of the mitogenic activity was immunoprecipitated by antibodies raised against platelet-derived growth factor (PDGF). Immunoblotting indicated a true molecular size of 32 kDa for this PDGF-like growth factor. Analysis of poly(A)+ RNA from Neuro-2A cells demonstrated the expression of the c-sis oncogene in this cell line, whereas in vitro translation of the RNA yielded a 20-kDa protein recognized by anti-PDGF antibodies. Separation by reverse-phase high-pressure liquid chromatography demonstrated the presence of two distinct mitogenic activities in neuroblastoma-derived transforming growth factor preparations, one of which is antigenically related to PDGF. Both activities had the ability to induce anchorage-independent growth in normal rat kidney cells, both in the presence and in the absence of epidermal growth factor. It is concluded that Neuro-2A cells express c-sis with concomitant production and secretion of a PDGF-like growth factor, which plays a role in the induction of phenotypic transformation on normal rat kidney cells.

scholarly journals Platelet Rich Fibrin (PRF) and Its Related Products: Biomolecular Characterization of the Liquid Fibrinogen

2020 ◽  
Vol 9 (4) ◽  
pp. 1099
Author(s):  
Giorgio Serafini ◽  
Mariangela Lopreiato ◽  
Marco Lollobrigida ◽  
Luca Lamazza ◽  
Giulia Mazzucchi ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Whole Blood ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Bone Morphogenetic Protein 2 ◽  
Time Points ◽  
Cell Counts ◽  
Tgf Β1

Liquid fibrinogen is an injectable platelet concentrate rich in platelets, leukocytes, and fibrinogen obtained by blood centrifugation. The aim of this study was to analyze the release of different growth factors in the liquid fibrinogen at different times and to assess possible correlations between growth factors and cell counts. The concentration of transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor-AB (PDGF-AB), platelet-derived growth factor-BB (PDGF-BB), bone morphogenetic protein 2 (BMP-2), fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF) released by liquid fibrinogen were examined with ELISA at three time points (T0, time of collection; T7, 7 days; T14, 14 days). The cellular content of the liquid fibrinogen and whole blood was also calculated for each volunteer. A mean accumulation of platelets of almost 1.5-fold in liquid fibrinogen compared to whole blood samples was found. An increase of TGF-β1, PDGF-AB, FGF-2, and VEGF levels was detected at T7. At T14, the level of TGF-β1 returned to T0 level; PDGF-AB amount remained high; the levels of FGF-2 and VEGF decreased with respect to T7, but remained higher than the T0 levels; PDGF-BB was high at all time points; BMP-2 level was low and remained constant at all time points. TGF-β1, PDGF-AB, and PDGF-BB showed a correlation with platelet amount, whereas BMP-2, FGF-2, and VEGF showed a mild correlation with platelet amount. Due to the high concentration of platelets, liquid fibrinogen does contain important growth factors for the regeneration of both soft and hard tissue. The centrifugation protocol tested in this study provides a valid solution to stimulate wound healing in oral and periodontal surgery.

scholarly journals High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma

1997 ◽  
Vol 83 (1) ◽  
pp. 120-128 ◽  
Author(s):  
John T. Berg ◽  
Zhenxing Fu ◽  
Ellen C. Breen ◽  
Hung-Cuong Tran ◽  
Odile Mathieu-Costello ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Wall Stress ◽  
Lung Parenchyma ◽  
Control Group ◽  
High Peep ◽  
Mrna Levels ◽  
Lung Inflation ◽  
Pulmonary Capillaries

Berg, John T., Zhenxing Fu, Ellen C. Breen, Hung-Cuong Tran, Odile Mathieu-Costello, and John B. West. High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma. J. Appl. Physiol. 83(1): 120–128, 1997.—Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for α1(III) and α2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-β1. In contrast, α2(I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma.

Circulating keratan sulfate as a marker of metabolic changes of cartilage proteoglycan in juvenile idiopathic arthritis; influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations

2015 ◽  
Vol 53 (2) ◽  
Author(s):  
Katarzyna Winsz-Szczotka ◽  
Katarzyna Komosińska-Vassev ◽  
Kornelia Kuźnik-Trocha ◽  
Andrzej Siwiec ◽  
Bogusław Żegleń ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Joint Damage ◽  
Keratan Sulfate ◽  
Control Group ◽  
Pretreatment Condition ◽  
Potential Marker ◽  
Tgf Β1

AbstractThe aim of this study was to evaluate the plasma keratan sulfate (KS) level as a potential marker of joint damage in children with juvenile idiopathic arthritis (JIA). The influence of growth factors as well as proteolytic and prooxidative agents on aggrecan alterations were evaluated in this study.Plasma levels of KS, transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS-4 and ADAMTS-5), and thiol groups (TG) were quantified in samples obtained from 30 healthy subjects and 30 patients with JIA before and after treatment.Increased (p<0.01) plasma KS was observed in JIA patients before treatment. Therapy resulted in a decrease in KS level. However, plasma KS level remained higher (p<0.05) than in controls. Increased levels of TGF-β1 (p<0.01) and PDGF-BB (p<0.05) in untreated JIA patients were recorded. Clinical improvement was accompanied by significant decrease in TGF-β1 and PDGF-BB, compared with a pretreatment condition and a control group. The concentrations of proteinases were characterized by different trends of alterations. When the ADAMTS-4 level increased (p<0.01) in the blood of untreated patients, the concentration of ADAMTS-5 was found to be reduced (p<0.0001), compared with controls. JIA treatment resulted in the normalization of ADAMTS-4 level. Plasma TG concentration was decreased only in untreated patients (p<0.05). We have revealed a significant correlation between plasma KS level and ADAMTS-4, TGF-β1, TG, C-reactive protein, and erythrocyte sedimentation rate levels.Plasma KS level in JIA patients, reflecting the aggrecan structure, indicates that treatment that modifies inflammation simultaneously does not contribute to total regeneration of articular matrix components and signalizes the need for further treatment.

scholarly journals Purification of a growth factor related to platelet-derived growth factor and a type β transforming growth factor secreted by mouse neuroblastoma cells. A general strategy for the purification of basic polypeptide growth factors

1989 ◽  
Vol 257 (2) ◽  
pp. 375-382 ◽  
Author(s):  
A J M Van den Eijnden-Van Raaij ◽  
I Koornneef ◽  
T M J Van Oostwaard ◽  
A Feyen ◽  
W Kruijer ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Gel Filtration ◽  
Platelet Derived Growth Factor ◽  
High Yield ◽  
General Strategy ◽  
Polypeptide Growth Factors ◽  
Mouse Neuroblastoma ◽  
Basic Polypeptide

A general strategy was developed for the purification of basic polypeptide growth factors. This method is a combination of gel filtration, weak-cation-exchange h.p.l.c. and reverse-phase h.p.l.c., separating the proteins according to size, charge and hydrophobicity respectively. All steps are carried out at low pH with exclusively volatile acidic buffer solutions. The sterile conditions and easy removal of salt by freeze-drying facilitate the detection of the growth factors by biological assays. By using this method, homogeneous preparations of two basic growth factors were purified in high yield from mouse-neuroblastoma-Neuro-2A-cell-conditioned medium. It is shown that these purified factors are biochemically and immunologically related to platelet-derived growth factor and type beta transforming growth factor from human platelets.

scholarly journals Platelet Derived Growth Factor-AA Correlates With Muscle Function Tests and Quantitative Muscle Magnetic Resonance in Dystrophinopathies

2021 ◽  
Vol 12 ◽  
Author(s):  
Alicia Alonso-Jiménez ◽  
Esther Fernández-Simón ◽  
Daniel Natera-de Benito ◽  
Carlos Ortez ◽  
Carme García ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Serum Concentration ◽  
Muscle Function ◽  
Transforming Growth Factor ◽  
Tissue Growth ◽  
Platelet Derived Growth Factor ◽  
Blood Samples ◽  
Function Tests ◽  
Fat Fraction

Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials.Methods: We collected clinical and functional data and blood samples from 19 DMD patients, 13 BMD patients, and 66 healthy controls (8 pediatric and 58 adult controls), and blood samples from 15 patients with dysferlinopathy (DYSF) and studied the serum concentration of 4 growth factors involved in the process of muscle fibrosis. We correlated the serum concentration of these growth factors with several muscle function tests, spirometry results and fat fraction identified by quantitative Dixon muscle MRI.Results: We found significant differences in the serum concentration of Platelet Derived Growth Factor-AA (PDGF-AA) between DMD patients and pediatric controls, in Connective Tissue Growth Factor (CTGF) between BMD patients and adult controls, and in and Transforming Growth Factor- β1 (TGF-β1) between BMD and DYSF patients. PDGF-AA showed a good correlation with several muscle function tests for both DMD and BMD patients and with thigh fat fraction in BMD patients. Moreover, PDGF-AA levels were increased in muscle biopsies of patients with DMD and BMD as was demonstrated by immunohistochemistry and Real-Time PCR studies.Conclusion: Our study suggests that PDGF-AA should be further investigated in a larger cohort of DMD and BMD patients because it might be a good biomarker candidate to monitor the progression of these diseases.

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