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See detailVascular Endothelial Growth Factor-111 (VEGF-111) and tendon healing: preliminary results in a rat model of tendon injury
Kaux, Jean-François ULg; Janssen, Lauriane ULg; Drion, Pierre ULg et al

in Muscle, Ligaments and Tendons Journal (2014), 1(5), 25-28

Tendon lesions are among the most frequent musculoskeletal pathologies. Vascular endothelial growth factor (VEGF) is known to regulate angiogenesis. VEGF-111, a biologically active and proteolysis ... [more ▼]

Tendon lesions are among the most frequent musculoskeletal pathologies. Vascular endothelial growth factor (VEGF) is known to regulate angiogenesis. VEGF-111, a biologically active and proteolysis-resistant splice variant of this family, was recently identified. This study aimed at evaluating whether VEGF-111 could have a therapeutic interest in tendon pathologies. Surgical section of one Achilles tendon of rats was performed before a local injection of either saline or VEGF-111. After 5, 15 and 30 days, the Achilles tendons of 10 rats of both groups were sampled and submitted to a biomechanical tensile test. The force necessary to induce tendon rupture was greater for tendons of the VEGF-111 group (p<0.05) while the section areas of the tendons were similar. The mechanical stress was similar at 5 and 15 days in the both groups but was improved for the VEGF-111 group at day 30 (p <0.001). No difference was observed in the mRNA expression of collagen III, tenomodulin and MMP-9. In conclusion, we observed that a local injection of VEGF-111 improves the early phases of the healing process of rat tendons after a surgical section. Further confirmatory experimentations are needed to consolidate our results. [less ▲]

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See detailADAMTS-3 deficiency is embryonic lethal in mouse and zebrafish.
Janssen, Lauriane ULg; Dubail, Johanne; Dupont, Laura ULg et al

Conference (2013, November)

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See detailNew prospects in the roles of the C-terminal domains of VEGF-A and their cooperation for ligand binding, cellular signaling and vessels formation.
Delcombel, Romain ULg; Janssen, Lauriane ULg; Vassy, Roger et al

in Angiogenesis (2013), 16(2), 353-71

VEGF-A is a crucial growth factor for blood vessel homeostasis and pathological angiogenesis. Due to alternative splicing of its pre-mRNA, VEGF-A is produced under several isoforms characterized by the ... [more ▼]

VEGF-A is a crucial growth factor for blood vessel homeostasis and pathological angiogenesis. Due to alternative splicing of its pre-mRNA, VEGF-A is produced under several isoforms characterized by the combination of their C-terminal domains, which determines their respective structure, availability and affinity for co-receptors. As controversies still exist about the specific roles of these exon-encoded domains, we systematically compared the properties of eight natural and artificial variants containing the domains encoded by exons 1-4 and various combinations of the domains encoded by exons 5, 7 and 8a or 8b. All the variants (VEGF(111)a, VEGF(111)b, VEGF(121)a, VEGF(121)b, VEGF(155)a, VEGF(155)b, VEGF(165)a, VEGF(165)b) have a similar affinity for VEGF-R2, as determined by Surface plasmon resonance analyses. They strongly differ however in terms of binding to neuropilin-1 and heparin/heparan sulfate proteoglycans. Data indicate that the 6 amino acids encoded by exon 8a must be present and cooperate with those of exons 5 or 7 for efficient binding, which was confirmed in cell culture models. We further showed that VEGF(165)b has inhibitory effects in vitro, as previously reported, but that the shortest VEGF variant possessing also the 6 amino acids encoded by exon 8b (VEGF(111)b) is remarkably proangiogenic, demonstrating the critical importance of domain interactions for defining the VEGF properties. The number, size and localization of newly formed blood vessels in a model of tumour angiogenesis strongly depend also on the C-terminal domain composition, suggesting that association of several VEGF isoforms may be more efficient for treating ischemic diseases than the use of any single variant. [less ▲]

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See detailEffects of platelet-rich plasma (PRP) on the healing of Achilles tendons of rats
Kaux, Jean-François ULg; Drion, Pierre ULg; Colige, Alain ULg et al

in Wound Repair & Regeneration : Official Publication of the Wound Healing Society and the European Tissue Repair Society (2012), 20(5), 748-756

Platelet-Rich Plasma (PRP) contains growth factors involved in the tissular healing process. The aim of the study was to determine if an injection of PRP could improve the healing of sectioned Achilles ... [more ▼]

Platelet-Rich Plasma (PRP) contains growth factors involved in the tissular healing process. The aim of the study was to determine if an injection of PRP could improve the healing of sectioned Achilles tendons of rats. After surgery, rats received an injection of PRP (n=60) or a physiological solution (n=60) in situ. After 5, 15 and 30 days, 20 rats of both groups were euthanized and 15 collected tendons were submitted to a biomechanical test using cryo-jaws before performing transcriptomic analyses. Histological and biochemical analyses were performed on the 5 remaining tendons in each group. Tendons in the PRP group were more resistant to rupture at 15 and 30 days. The mechanical stress was significantly increased in tendons of the PRP group at day 30. Histological analysis showed a precocious deposition of fibrillar collagen at day 5 confirmed by a biochemical measurement. The expression of tenomodulin was significantly higher at day 5. The mRNA level of type III collage, matrix metalloproteinase 2, 3 and 9 was similar in the 2 groups at all time points whereas type I collagen was significantly increased at day 30 in the PRP group. In conclusion, an injection of PRP in sectioned rat Achilles tendon influences the early phase of tendons healing and results in an ultimate stronger mechanical resistance. [less ▲]

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See detailEffects of platelet-rich plasma on the healing of tendons: animal model
Kaux, Jean-François ULg; Drion, Pierre ULg; Colige, Alain ULg et al

in Biomedica 2012 (2012, April)

Introduction: Platelet-Rich Plasma (PRP) contains lot of growth factors which could enhance the healing process of different tissues. We aimed to determine if a single injection of PRP could improve the ... [more ▼]

Introduction: Platelet-Rich Plasma (PRP) contains lot of growth factors which could enhance the healing process of different tissues. We aimed to determine if a single injection of PRP could improve the cicatrisation of ruptured Achilles tendons of rats. Material and Methods: A 5mm defect was surgically made in the Achilles tendon of 120 rats. A few hours after surgery, 45 rats received a PRP or PBS injection in situ. After 5, 15 and 30 days, 20 rats of both groups were euthanized and 15 collected tendons were immediately submitted to a biomechanical tensile strength test until rupture using a “cryo-jaw” device. After, theses samples were used for transcriptomic analyses. Histological and biochemical analyses were performed on the five remained tendons in each group. Results: Tendons in the PRP group were more resistant to rupture at 15 and 30 days than those in the control group. The transverse area of tendons in the PRP group was significantly higher at day 5 and 15. The constraint was significantly increased in tendons of the PRP group in the late phase of the healing (day 30). Histological and immunohistological analysis showed an increased staining for fibrillar collagen at day 5 confirmed by a biochemical analysis showing an increased collagen concentration in the callus. The expression of tenomodulin, a tenocyte differentiation marker, was significantly higher in the PRP-treated tendons at day 5. No significant difference in terms of mRNA for type III collagen and matrix metalloproteinase 9 was observed at any time between the 2 groups. Conclusion: A single injection of PRP in sectioned Achilles tendon of rats few hours after surgery influences the early phase of tendons healing, resulting in an ultimate stronger mechanical resistance. [less ▲]

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See detailIsoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation
Labied, Soraya ULg; Delforge, Yves ULg; Blacher, Silvia ULg et al

in Journal of Assisted Reproduction & Genetics (2012), 28(11), 1009

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See detailEvaluation of the use of VEGF111 for the treatment of tendon lesions.
Janssen, Lauriane ULg; Kaux, Jean-François ULg; Drion, Pierre ULg et al

Poster (2011, May 20)

Alterations of tendons are common pathologies resulting from repetitive or abnormal mechanical sollicitations. Very frequently lesions become chronic and may even lead to rupture. As there is no current ... [more ▼]

Alterations of tendons are common pathologies resulting from repetitive or abnormal mechanical sollicitations. Very frequently lesions become chronic and may even lead to rupture. As there is no current efficient treatment for curing this type of diseases, new therapeutic approaches are being tested and developed. Injection of platelet-rich plasma (PRP) seems to be a promising treatment by local release of growth factors. Among these factors, VEGF-A is known to induce positive effects on vascular functions and angiogenesis, and could be implicated in the healing process of tendons. Several isoforms of VEGF-A have been described in literature, including VEGF165 and 121. VEGF111 is encoded by exons 1-4 and 8a. The lack of exon 5 enables VEGF111 to resist to proteolytic degradation and the absence of exons 6 and 7 reduces its affinity for several macromolecules present on the cell surface and in the extracellular matrix. In vivo, it has been shown to be highly proangiogenic and diffusible. A 5mm defect was surgically performed in the Achilles tendon of 60 rats. Two hours after closure of the fascia and the skin, an injection within the wound was performed with PBS alone (n=30) or with PBS containing 100 ng of VEGF111 (n=30). 10 rats of each group were sacrificed at days 5, 15 and 30. The operated tendon was then carefully removed and collected for either immunohistochemical analyses or mechanical testing. At each time point, the section and the overall appearance of the repairing tendons were similar for PBS and VEGF111-injected tendon. As compared to controls, injection of VEGF111 seemed to promote a faster angiogenesis, although the number of samples was at this stage too low for performing reliable statistical analysis. Mechanical resistance to rupture of the repairing tendons was also measured. No difference between the two groups was observed after 5 or 15 days. By contrast, increased tensile strength was clearly evidenced in the VEGF-treated group after 30 days. These preliminary data seem to indicate a positive effect of a single VEGF111 injection for restoring the mechanical properties of tendons after their section. Additional experiments are planned for confirmation purposes and for further characterizing the model. It includes a “dose- response” analysis, the use of VEGF165 as an additional control and a study evaluating the effect of several injections. [less ▲]

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See detailTendon lesion and VEGF-111 injection
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

Poster (2010, November 25)

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments ... [more ▼]

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Injection of platelet-rich plasma (PRP) seems to be a promising one by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could be implicated in the healing process of tendons. Recently, a novel VEGF-A isoform was identified, the VEGF-111, a biologically active and proteolysis-resistant VEGF-A isoform, also known to present beneficial effects on ischemic diseases. This prompted us to evaluate whether VEGF-111 would have a therapeutic interest within the framework of the tendon pathology. Methods: 60 Rats were divided into 2 groups: A: control (no injection), B: VEGF-111 treatment. A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats received a local injection of VEGF-111 (100ng) in situ after the surgery and were placed in their cages without immobilization. After 5, 15 and 30 days, the traumatized Achilles tendons of 10 rats of both groups were removed and dissected during their healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Rats were then euthanized. Statistical analyses were made with an ANOVA. Values are significant when p-value is below 0.05. Results: Our results showed that the developed force necessary to induce tendon rupture during biomechanical tensile test was greater for tendons which had received an injection of 100ng of VEGF-111. These results were already noticed from day 5 onwards. The ratio between force and weight increased with time in both groups, but this ratio was greater for tendons which had been submitted to an injection of VEGF111. The surface area of the section of the tendons increased between 5 and 15 days followed by a stabilization. After 30 days, sections in both groups were similar. Thus, the constraint was similar after 5 and 15 days but was better for VEGF111 group after one month. Discussion - Conclusion: This experimentation has shown that a 100ng injection of VEGF-111 stimulated tendon healing process as suggested by the increased force needed to break tendons during its healing process and the increased of constraint in comparison with the control group. Other experimentations with different concentration of VEGF111 are now in process. Acknowledgement : This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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