Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto hydroxyapatite coatings: A comparative study

Brigaud, Isabelle; Agniel, Rémy; Leroy-Dudal, Johanne; Kellouche, Sabrina; Ponche, Arnaud; Bouceba, Tahar; Mihăilescu, Natalia; Sopronyi, Mihai; Viguier, É.; Ristoscu, Carmen; Sima, Félix; Carreira, Ana Cláudia Oliveira; Sogayar, Mari Cleide; Gallet, Olivier; Anselme, Karine

doi:10.1016/j.actbio.2017.04.013

Cited by 40 publications

(48 citation statements)

References 64 publications

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“…Further, at the dose of BMP2 used, we also confirmed the additive effects of PEMFs and BMP2 on all the parameters investigated. Then, in order to investigate the molecular events related to BMP signaling pathway during cell differentiation induced by BMP2, PEMFs, or both stimuli used in combination, we first analyzed the effects on the gene expression of several components of the BMP signaling pathway including other BMPs with high osteogenic potential and their receptors [15,17,18,20]. Among the BMPs investigated, the significant changes observed included a significant increase in BMP6 expression (3 days) and in BMP2 (28 days) in cells treated with BMP2 and PEMFs used in combination, compared to cells cultured in OM.…”

Section: Discussionmentioning

confidence: 99%

“…In order to investigate the potential effects of PEMF exposure on BMP signaling, we evaluated the gene expression of several components belonging to the BMP signaling pathway including BMP2, BMP6, and BMP9 which are known to induce the most potent osteogenic differentiation of MSCs and the main receptors involved in BMP signaling including BMP type I (ALK2/ACVR1, ALK3/BMPR-IA, and ALK6/BMPR-IB) and type II (BMPR-II) receptors [15,17,18,20] in cells undergoing osteogenic differentiation in all our experimental conditions. Target genes showing significant differences in their expression at any time during cell differentiation are reported in Figure 3.…”

Section: Effects Of Pemf Exposure and Bmp2 On Gene Expression Of Bmpsmentioning

confidence: 99%

“…Actually, more than 20 BMPs have been identified. Among them, BMP-2, -4, -6, -7, and -9 play major roles in bone morphogenesis [16,18,20]. Notably, recombinant human BMP-2 (rhBMP2), produced by a genetically engineered Chinese hamster ovary (CHO) cell line, was the first to be introduced as a bone graft substitute and received Food and Drug Administration approval in 2002 [19].…”

Section: Introductionmentioning

confidence: 99%

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Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

Martini

Pellati

Mazzoni

et al. 2020

IJMS

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Pulsed electromagnetic fields (PEMFs) are clinically used with beneficial effects in the treatment of bone fracture healing. This is due to PEMF ability to favor the osteogenic differentiation of mesenchymal stem cells (MSCs). Previous studies suggest that PEMFs enhance the osteogenic activity of bone morphogenetic protein-2 (BMP2) which is used in various therapeutic interventions. This study investigated the molecular events associated to the synergistic activity of PEMFs and BMP2 on osteogenic differentiation. To this aim, human MSCs (hMSCs) were exposed to PEMFs (75 Hz, 1.5 mT) in combination with BMP2, upon detection of the minimal dose able to induce differentiation. Changes in the expression of BMP signaling pathway genes including receptors and ligands, as well as in the phosphorylation of BMP downstream signaling proteins, such as SMAD1/5/8 and MAPK, were analyzed. Results showed the synergistic activity of PEMFs and BMP2 on osteogenic differentiation transcription factors and markers. The PEMF effects were associated to the increase in BMP2, BMP6, and BMP type I receptor gene expression, as well as SMAD1/5/8 and p38 MAPK activation. These results increase knowledge concerning the molecular events involved in PEMF stimulation showing that PEMFs favor hMSCs osteogenic differentiation by the modulation of BMP signaling components.

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Section: Discussionmentioning

confidence: 99%

Section: Effects Of Pemf Exposure and Bmp2 On Gene Expression Of Bmpsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

Martini

Pellati

Mazzoni

et al. 2020

IJMS

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“…Several lines of evidence have demonstrated that BMPs can regulate the level of chondrocyte proliferation and differentiation (Minina et al, ). In addition, most BMPs, including BMP6 and BMP7, are able to stimulate osteogenesis in premature or mature osteoblasts (Brigaud et al, ). In the present study, the expression of BMP6 in hindlimbs of B. gargarizans was gradually increased during the metamorphosis, whereas BMP7 was decreased.…”

Section: Discussionmentioning

confidence: 99%

Endochondral ossification in hindlimbs during bufo gargarizans metamorphosis: A model of studying skeletal development in vertebrates

Gao

Zhang

Wang

2018

Developmental Dynamics

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Background Endochondral ossification, the process by which most of the skeleton is formed, is accurately regulated by many specific groups of molecules and extracellular matrix components. The molecular mechanisms of endochondral ossification have been extensively investigated in mammals. However, there are few studies about it in amphibians. Results Ossification of femur and tibiofibula was observed at Gs 40, and tarsals and metatarsals were ossified at Gs 42. Most of the skeletons in hindlimbs were completely ossified except for articular cartilages at Gs 46. Thirty-two genes related to endochondral ossification were found in the differentially expressed genes (DEGs) library of hindlimbs, and nine of these genes were validated by qRT-PCR during metamorphosis. Sox9 was expressed in the columnar, prehypertrophic, and upper hypertrophic zones, and the expression of Ihh was observed in prehypertrophic chondrocyte zone in hindlimbs of B. gargarizans. Conclusions The ossification of hindlimbs increased gradually, and the ossification sequence was from proximal to distal in B. gargarizans during metamorphosis. Thirty-two genes found in the DEGs library were related to the regulation of endochondral ossification of hindlimbs in amphibians. The present study will provide a valuable genomic resource for the future study of endochondral ossification in amphibian. Developmental Dynamics 247:1121-1134, 2018. © 2018 Wiley Periodicals, Inc.

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“…While BMP-7 is emerging as a regulator of cell adhesion and migration by modulating β-integrin activation [9] and by inducing the expression of α5 integrins [10], the interplay between BMP-6-mediated signaling and cell adhesion to the extracellular matrix remains largely unexplored. When combined with fibronectin, BMP-6 osteogenic activity is prolonged [11], suggesting that BMP-6 matrix interactions participate in the regulation of cell fate. Furthermore, BMP-6 signaling activity, which results in the phosphorylation of the Smad 1/5/8 complex, appears to be modulated by the interactions of the growth factor with heparin.…”

Section: Introductionmentioning

confidence: 99%

Copresentation of BMP-6 and RGD Ligands Enhances Cell Adhesion and BMP-Mediated Signaling

Posa

Grab

Martin

et al. 2019

Cells

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We report on the covalent immobilization of bone morphogenetic protein 6 (BMP-6) and its co-presentation with integrin ligands on a nanopatterned platform to study cell adhesion and signaling responses which regulate the transdifferentiation of myoblasts into osteogenic cells. To immobilize BMP-6, the heterobifunctional linker MU-NHS is coupled to amine residues of the growth factor; this prevents its internalization while ensuring that its biological activity is maintained. Additionally, to allow cells to adhere to such platform and study signaling events arising from the contact to the surface, we used click-chemistry to immobilize cyclic-RGD carrying an azido group reacting with PEG-alkyne spacers via copper-catalyzed 1,3-dipolar cycloaddition. We show that the copresentation of BMP-6 and RGD favors focal adhesion formation and promotes Smad 1/5/8 phosphorylation. When presented in low amounts, BMP-6 added to culture media of cells adhering to the RGD ligands is less effective than BMP-6 immobilized on the surfaces in inducing Smad complex activation and in inhibiting myotube formation. Our results suggest that a local control of ligand density and cell signaling is crucial for modulating cell response.

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Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto hydroxyapatite coatings: A comparative study

Cited by 40 publications

References 64 publications

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

Endochondral ossification in hindlimbs during bufo gargarizans metamorphosis: A model of studying skeletal development in vertebrates

Copresentation of BMP-6 and RGD Ligands Enhances Cell Adhesion and BMP-Mediated Signaling

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