Biological and binding studies of acidic fibroblast growth factor in the presence of substituted dextran

Tardieu, M; Slaoui, Faouzi; Josefonvicz, Jacqueline; Courty, José; Gamby, Chantal; Barritault, Denis

doi:10.1163/156856289x00064

Cited by 28 publications

(16 citation statements)

References 23 publications

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“…The purified derivatized dextran was ultrafiltered and analyzed. The chemical composition was deter mined by microanalysis, and spectrophotometry as already described [19]. In the present study, the methyl carboxylic acid content was 110%, the benzylamide content was 2.5%, and the sulfonate content was 36.5%.…”

Section: Cmdbs Synthesis and Characterization O F The Moleculesupporting

confidence: 50%

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CMDBS, Functional Analogue of Heparin Sulfate as a New Class of Corneal Ulcer Healing Agents

Fredj-Reygrobellet¹,

Hristova²,

Ettaiche³

et al. 1994

Ophthalmic Res

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Soluble dextran polymer derivatives (CMDBSs) are originally synthesized as heparin-like plasma substitutes. Some of them mimic heparin in its interactions and stabilize, protect and facilitate actions of heparin binding growth factors. The wound healing activity of one specific CMDBS was studied in a model of corneal ulcer on the rabbit eye and compared with the activity of basic fibroblast growth factors (bFGF) added alone or in association with CMDBS. Total reepithelialization was observed with bFGF + CMDBS, bFGF alone and CMDBS alone after, respectively, 3.8 ± 0.78, 4.3 ± 0.67 and 4.4 ± 0.51 days. All treatments were efficient if compared with eyes treated with saline (p < 0.0001). The grade of significance of the applied treatments was as follows: bFGF + CMDBS > bFGF > CMDBS > saline. Our study pinpoints that some specific CMDBS are as potent agents as bFGF for corneal ulcer healing, and can therefore be proposed for therapeutic use.

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Section: Cmdbs Synthesis and Characterization O F The Moleculesupporting

confidence: 50%

“…A water-soluble dextran derivative was prepared from dextran T40, batch 32202 (Pharmacia Fine Chemicals, Uppsala, Sweden) as previously described [19]. The purified derivatized dextran was ultrafiltered and analyzed.…”

Section: Cmdbs Synthesis and Characterization O F The Moleculementioning

confidence: 99%

CMDBS, Functional Analogue of Heparin Sulfate as a New Class of Corneal Ulcer Healing Agents

Fredj-Reygrobellet¹,

Hristova²,

Ettaiche³

et al. 1994

Ophthalmic Res

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“…They were selected for their ability (1) to interact with and protect some heparin-binding growth factors (HBGFs) against heat, acid and proteolytic degradation, and (2) to modify the phenotypic expression of various cell types [Tardieu et al, 1989[Tardieu et al, , 1992Letourneur et al, 1993], including human Accepted after revision: October 27, 1998 ¤Abbreviations used in this paper HBGF heparin-binding growth factor PBS phosphate-buffered saline MNGC multinucleated giant cell RGTA regenerating agent osteoblasts [Berrada et al, 1994]. Thus, RGTAs mimic the properties of heparan sulfate proteoglycans towards HBGFs [Gospodarowicz and Cheng, 1986;Paralkar et al, 1990;McCaffrey et al, 1994].…”

Section: Rgtamentioning

confidence: 99%

A Single Low Dose of RGTA<sup>®</sup>, a New Healing Agent, Hastens Wound Maturation and Enhances Bone Deposition in Rat Craniotomy Defects

Colombier

Lafont

Blanquaert

et al. 1999

Cells Tissues Organs

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RGTA^®, a new family of dextran-derived healing agents, promotes the repair of various tissues, including bone. In this study, we examined whether a dose of RGTA lower than in our previous studies could still modify the healing pattern in craniotomy defects. In 24 rats, two defects (3 mm diameter) were drilled on either side of the calvaria sagittal suture. The right defect was filled with a piece of collagen soaked with RGTA in phosphate-buffered saline (PBS; 4 μg/ml), and the left one with collagen soaked in PBS only. After 7, 14 and 21 days, the calvaria were removed and processed for histometry. On day 7, in contrast with the control defects, the treated sites were inflammation-free and centripetal bone plates had started to grow. By day 14, the bone filling was significantly enhanced in the treated defects (+ 290%, p < 0.05), and isolated bone nodules had formed within the fibrous connective tissue (= fibrous hammock) joining the defect edges. The hammock had already differentiated by day 7 in all the RGTA-treated defects, and it was significantly thicker on days 14 (+ 190%, p < 0.05) and 21 (+ 139%, p < 0.05). The colonization of the hammock by mast cells was increased in the treated sites (+ 320%, p < 0.05 on day 21). On day 7, most of the bony edges of the treated defects had been resorbed by osteoclasts, while the process only started in the controls. These data indicate that a low dose of RGTA modified the cascade of events occurring at the initial stages of repair, so that the tissular maturation of the treated defects was more rapid. In fact the use of RGTA in the wounds provoked a shift from a fibrous repair as seen in the controls, to a bone reconstruction favoring defect closure.

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“…6 RGTAs correspond to a family of heparan-like polymers, synthesized from dextran by a sequential substitution of carboxymethyl, benzylamide, and sulfonate groups on its glucose units, that were shown to mimic in vitro some heparin or heparan sulfates properties relative to fibroblast growth factors (FGFs) and transforming growth factor-␤1 (TGF-␤1). 3,7,8 Heparin, heparan sulfates, and heparan and chondroitin sulfate proteoglycans are known to protect growth factors characterized by their high affinity for heparin, also called heparin-binding growth factors (HBGFs), from proteolytic degradations and to potentiate their in vitro biologic effects. 9 These molecules, found in the extracellular matrix and on the cell surface, act as a reservoir of HBGFs and therefore can contribute to the release of bioavailable HBGFs in injured sites and ensure the long-term effects of these factors.…”

Section: Introductionmentioning

confidence: 99%

RGTA modulates the healing pattern of a defect in a monolayer of osteoblastic cells by acting on both proliferation and migration

Blanquaert

Carpentier

Morvan

et al. 2003

J Biomedical Materials Res

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A family of heparan-like polymers, RGTAs, was shown to promote repair of various tissues. Like heparin and heparan-sulfates, RGTAs potentiate in vitro the biological activities of heparin-binding growth factors (HBGFs) and protect them against proteolytic degradation. It was postulated that RGTAs stimulate bone healing by interacting with HBGFs released in the wound site and, subsequently, by promoting the proliferation of cells implicated in this process. In a previous report, we examined how RGTA can modulate the proliferation of MC3T3-E1 osteoblastic cells. To further complete this study and to support this hypothesis, we developed an in vitro model of bone repair and examined the effects of RGTA alone or in association with FGF2, BMP-2, and TGF-beta1 which are representative of HBGFs known to stimulate bone repair. The model consisted of a 6-mm reproducible defect created on a MC3T3-E1 cell monolayer. In the presence of the different products added to the medium, the process of wound repair was measured through the filling of the acellular defect. We show that in 8 days, RGTA slightly inhibits repair alone compared to the control (2% FBS), that it inhibits the mitogenic effect of FGF2, and that it amplifies the inhibitory effect of BMP-2 and TGF-beta1. Repair was realized by an association of cell migration and cell proliferation mechanisms. To determine the part played by each process, DNA synthesis was evaluated for cell proliferation using an immunodetection technique [to measure incorporation of 5-bromo-2-deoxyuridine (BrdU)], coupled with a computer-assisted image analysis. The results show that the presence of RGTA (1) amplified the number of labeled nuclei compared to the control, (2) added to FGF2 or TGF-beta1, it reduced the number of labeled nuclei compared to FGF2 or TGF-beta1 alone, and (3) in the presence of BMP-2, it amplified the number of labeled nuclei compared to BMP-2 alone. Proper interpretation of these data requires a better understanding of the mechanism of action of RGTA on bone healing.

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Biological and binding studies of acidic fibroblast growth factor in the presence of substituted dextran

Cited by 28 publications

References 23 publications

CMDBS, Functional Analogue of Heparin Sulfate as a New Class of Corneal Ulcer Healing Agents

CMDBS, Functional Analogue of Heparin Sulfate as a New Class of Corneal Ulcer Healing Agents

A Single Low Dose of RGTA<sup>®</sup>, a New Healing Agent, Hastens Wound Maturation and Enhances Bone Deposition in Rat Craniotomy Defects

RGTA modulates the healing pattern of a defect in a monolayer of osteoblastic cells by acting on both proliferation and migration

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