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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 Muscles, Ligaments and Tendons Journal (2014), 4(1), 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 detailEmerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data.
Hulin, Alexia; Deroanne, Christophe ULg; Lambert, Charles ULg et al

in Cardiovascular Pathology (2013), 22

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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 detailGenome-wide analysis of the effect of heavy ions bombardment on gene expression and alternative splicing by neuronal cells.
Lambert, Charles ULg; Ernst, Eric; Quintens, R et al

Conference (2012, June 18)

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See detailPlatelet-rich plasma (PRP) and tendon healing: animal model
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in British Journal of Sports Medicine (2011, February), 45(2), 1

Introduction: The tendon is a tissue which does not heal easily. Recently, several studies have demonstrated the positive effects of platelets on the healing process of tendons. A local injection of ... [more ▼]

Introduction: The tendon is a tissue which does not heal easily. Recently, several studies have demonstrated the positive effects of platelets on the healing process of tendons. A local injection of platelet–rich plasma (PRP), which releases in situ many growth factors, has the potentiality to enhance the tendon healing process. The aim of our experiment was to ascertain by an original mechanical measure whether the use of PRP was of interest for accelerating the healing process of rats’ Achilles tendons after surgical induced lesion. Methods: A 5mm defect was surgically induced in 90 rats’ Achilles tendon. Rats were divided into 2 groups of 45: (A) control (no treatment) and (B) PRP treatment. Rats of group B received a PRP injection in situ after the surgery. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 traumatized Achilles tendons of each group were dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. After that, transcriptomic analyses were made on the tendon samples, to study the expression of type III collagen, matrix metalloproteases and tenomodulin. A hydroxyproline dosage was done to quantify the collagen in the tendon during its healing process. Tendons of the 15 remaining rats of each group were subjected to a histological study, respectively at day 5, 15 and 30 (5 rats for each time). Results: We demonstrated that the force necessary to induce tendon rupture during biomechanical tensile test study was greater for tendons which had been submitted to an injection of PRP compared to the control group: +19% (day 5), +30% (day 15) and +43% (day 30). Histological study showed that PRP could enhance cells proliferation, angiogenesis and collagen organisation. Our biochemical analyses did not explain beneficial effects of PRP. Indeed, there was no significant difference neither between the expression of different studied genes, nor in the quantity of hydroxyproline between both groups. Conclusion: This experimentation has shown that a PRP injection could accelerate the tendons healing process and improve its quality. [less ▲]

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See detailTendon lesion and platelet-rich plasma (PRP) injection: rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in Annual Congress of the RBSPRM (2010, December 03)

Introduction: For a few years, the positive effect of platelets on the healing process of different tissues (skin, bones...) was demonstrated. In fact platelets contain lots of growth factors which can be ... [more ▼]

Introduction: For a few years, the positive effect of platelets on the healing process of different tissues (skin, bones...) was demonstrated. In fact platelets contain lots of growth factors which can be release locally and enhance the healing process. Thus the aim of our experiment was to ascertain by an original mechanical measure whether the use of PRP was of interest for accelerating the healing process of rats’ Achilles tendons after surgical induced lesion. Methods: Ninety rats’ Achilles tendons were sectioned. Forty-two rats beneficed of a PRP injection in situ. After 5, 15 and 30 days, 15 rats of both groups were euthanized after tendon sampling which were immediately submitted to a biomechanical tensile test until tendon rupture, using an original method of measurement (“cryo-jaw”). Histological and biochemical analyses were made as well as a quantification of collagen with an original procedure (quantification of the “greys” on histological cross-sections). Results: Tendons in the PRP group were more resistant to rupture than those in the control group. Histological findings showed in this group an increase of collagen proliferation and better collagen fibres reorganization. However, we did not find any biochemical difference neither in term of encoding gene expression for type III collagen, matrix metalloprotease 9 and tenomodulin. Conclusion: Our animal study demonstrated that an injection of PRP could accelerate the tendons healing process and improve its quality. [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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See detailTendon lesion and platelet-rich plasma (PRP) injection
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

Poster (2010, November 25)

Introduction: For a few years, the positive effects of platelets on the healing process of different tissues (skin, bones...) were demonstrated. In fact platelets contain lots of growth factors which can ... [more ▼]

Introduction: For a few years, the positive effects of platelets on the healing process of different tissues (skin, bones...) were demonstrated. In fact platelets contain lots of growth factors which can be release locally and enhance the healing process. Thus the aim of our experiment was to ascertain by an original mechanical measure whether the use of PRP was of interest for accelerating the healing process of rats’ Achilles tendons after surgical induced lesion. Methods: A 5mm defect was surgically induced in 90 rats’ Achilles tendon. Rats were divided into 2 groups of 45: (A) control (no treatment) and (B) PRP treatment. Rats of group B received a PRP injection in situ after the surgery. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 traumatized Achilles tendons of each group were dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. After that, transcriptomic analyses were made on the tendon samples, to study the expression of type III collagen, matrix metalloproteases and tenomodulin. A hydroxyproline dosage was finally realised to quantify the collagen in the tendon during its healing process. Tendons of the 15 remaining rats of each group were subjected to a histological study, respectively at day 5, 15 and 30 (5 rats for each time). Results: We demonstrated that (1) the stress (F) during biomechanical tensile test up to tendon rupture was significantly greater for tendons which had been submitted to an injection of PRP compared to the control group; (2) the surface (S) area of the section of the tendon was greater in the PRP group during the 15 first days, but this section was similar after 30 days in the 2 groups; (3) the ration F/weight of the rat was significantly greater in the PRP group at each time; (4) constrain was similar after the 15 first days but was significantly greater in the PRP group after 30 days. Histological study showed that PRP could enhance cells proliferation, angiogenesis and collagen organisation. Our biochemical analyses did not explain beneficial effects of PRP. Indeed, there was no significant difference between the expressions of different studied genes. Conclusion: Our animal study demonstrated that an injection of PRP could accelerate the tendons healing process and improve its quality. [less ▲]

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See detailInjection de concentrés plaquettaires et régénération tendineuse : modèle animal
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in 3ème Congrès Commun SFMS - SFTS (2010, October 01)

Introduction : La régénération tendineuse en traumatologie du sport demeure un processus actuellement difficile à gérer et de nouvelles voies thérapeutiques sont en cours d’exploration. La littérature ... [more ▼]

Introduction : La régénération tendineuse en traumatologie du sport demeure un processus actuellement difficile à gérer et de nouvelles voies thérapeutiques sont en cours d’exploration. La littérature récente fait état d’effets bénéfiques sur la régénération tendineuse de concentrés plaquettaires (platelet-rich plasma ou PRP), administrés in situ, dus au relargage de facteurs de croissance par activation des plaquettes et à leur activité stimulante au cours de la cicatrisation. Dès lors, nous avons souhaité tester l’effet bénéfique de ce traitement sur des rats préalablement lésés au niveau de leur tendon d’Achille. Matériel et Méthode : Une section unilatérale du tendon d’Achille a été réalisée chez 60 rats Sprague Dawley adultes. De ces 60 rats, 30 ont subi une cicatrisation naturelle (rats contrôles) et 30 rats ont bénéficié d’une injection in situ de PRP le jour de la lésion. Diverses études biomécaniques, biochimiques et histologiques ont été réalisées sur ces tendons d’Achille en cours de cicatrisation à respectivement J5, J15 et J30 après lésion. Dix rats supplémentaires ont servi de témoins sains (sans lésion tendineuse). L’étude biomécanique appréciait la résistance maximale des tendons à la traction à l’aide de mors type « cryo-jaws ». L’étude histologique évaluait l’évolution cellulaire pendant la phase de cicatrisation. L’analyse transcriptomique étudiait l’expression de gènes codant pour le collagène de type III, les métalloprotéases matricielles (MMP-9) et la ténomoduline (TNMD), ainsi qu’un dosage d’hydroxyproline permettant d’évaluer la quantité de collagène présente dans le tendon au cours de la cicatrisation. Résultats : L’étude biomécanique démontre la meilleure résistance des tendons traités avec du PRP par rapport aux tendons contrôles à J5 (+19%), J15 (+30%) et significativement à J30 (+43%). L’étude histologique suggère qu’une injection de PRP stimule la prolifération cellulaire, favorise l’organisation tissulaire, stimule l’angiogenèse et la réorganisation architectural du collagène. L’étude biochimique ne permet pas d’expliquer les effets bénéfiques puisqu’il n’y a pas de différence dans l’expression des gènes des différentes molécules matricielles (collagène de type III, MMP-9 et TNMD) ni dans la quantité d’hydroxyproline qui s’accroit au cours du temps de la cicatrisation de façon similaire dans les deux groupes. Conclusion : L’injection de PRP améliore et accélère la cicatrisation tendineuse et augmente la résistance aux contraintes mécaniques du tendon en cours de cicatrisation. [less ▲]

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See detailRepetitive intrathecal VEGF165 treatment has limited therapeutic effects after spinal cord injury in the rat.
van Neerven, Sabien; Joosten, Elbert A.J.; Brook, Gary A. et al

in Journal of Neurotrauma (2010), 27

Detailed reference viewed: 28 (1 ULg)