Comparison of Recombinant Growth/Differentiation Factor-5 (rGDF-5) and Bone Morphogenetic Protein-2 (rBMP-2) in the In Vivo Bone Formation in Porous Hydroxyapatite Ceramic

2005 ◽  
Vol 284-286 ◽  
pp. 945-948
Author(s):  
H. Shimaoka ◽  
Y. Dohi ◽  
K. Narikawa ◽  
Hajime Ohgushi ◽  
M. Ikeuchi ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
De Novo ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Potential ◽  
Differentiation Factor ◽  
Morphogenetic Protein ◽  
Growth Differentiation Factor 5

Various recombinant growth factors have been used for promoting osteoblastic differentiation cascade. To compare the growth/differentiation factor-5 (GDF-5) and bone morphogenetic protein-2 (BMP-2) in the in vivo osteogenic potential of bone marrow mesenchymal stem cells (MSCs), the bone formation was assessed by rat subcutaneous implantation of 5 kinds of hydroxyapatite (HA) implants; namely GDF/HA composites, BMP/HA composites, MSCs/HA composites and the MSCs/HA composites supplemented with recombinant mouse GDF-5 (GDF/MSCs/HA) or recombinant human BMP-2 (BMP/MSCs/HA). Neither the GDF/HA nor the BMP/HA composites exhibited any bone formation at any time after implantation. At both 2 and 4 weeks after implantation, obvious de novo bone formation together with active osteoblasts was seen histologically in many pores of the GDF/MSCs/HA and BMP/MSCs/HA composites. The GDF/MSCs/HA and BMP/MSCs/HA composites also showed high alkaline phosphatase (ALP) and osteocalcin expression determined at both the protein and gene levels. Compared with GDF/MSCs/HA, the BMP/MSCs/HA composites exhibited excellent osteogenesis with relatively early osteoblastic phenotype expression. These findings indicate that the two growth factors synergistically enhance de novo bone formation capability of MSCs/HA composites and the importance of ceramic surface to retain and to deliver the molecules of growth factors for the cell differentiation and maturation.

Bone Morphogenetic Protein 2 and Retinoic Acid Accelerate in Vivo Bone Formation, Osteoclast Recruitment, and Bone Turnover

2005 ◽  
Vol 11 (3-4) ◽  
pp. 645-658 ◽  
Author(s):  
Catherine M. Cowan ◽  
Oliver O. Aalami ◽  
Yun-Ying Shi ◽  
Yu-Fen Chou ◽  
Carina Mari ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
In Vivo Bone Formation

scholarly journals Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo

2007 ◽  
Vol 42 (3) ◽  
pp. 267-273 ◽  
Author(s):  
J. D. Bradley ◽  
D. G. Cleverly ◽  
A. M. Burns ◽  
N. B. Helm ◽  
M. J. Schmid ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Cyclooxygenase 2 ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

scholarly journals Umbilical Cord Mesenchymal Stem Cell-Derived Nanovesicles Potentiate the Bone-Formation Efficacy of Bone Morphogenetic Protein 2

2020 ◽  
Vol 21 (17) ◽  
pp. 6425
Author(s):  
Songhyun Lim ◽  
Hao-Zhen Lyu ◽  
Ju-Ro Lee ◽  
Shi Huan Han ◽  
Jae Hyup Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Umbilical Cord ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Calvarial Defects ◽  
In Vivo Bone Formation

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is one of the most potent osteogenic factors used to treat bone loss. However, at higher doses, rhBMP-2 does not necessarily increase bone formation but rather increases the incidence of adverse side effects. Here, we investigated whether umbilical cord mesenchymal stem cell (UCMSC)-derived nanovesicles (NVs) further increase the in vivo bone formation at high doses of rhBMP-2. In the presence of UCMSC-derived NVs, proliferation, migration, and tube formation of human umbilical vein endothelial cells were stimulated in vitro. Furthermore, migration and osteogenesis of human bone marrow-derived mesenchymal stem cells were stimulated. To examine the efficacy of UCMSC-derived NVs on in vivo bone formation, collagen sponges soaked with rhBMP-2 and UCMSC-derived NVs were used in athymic nude mice with calvarial defects. At a high rhBMP-2 dosage (500 ng/mL), UCMSC-derived NVs significantly promoted bone formation in calvarial defects; however, the UCMSC-derived NVs alone did not induce in vivo bone formation. Our results indicate that UCMSC-derived NVs can potentiate the bone formation efficacy of rhBMP-2 at a high dosage.

Bone morphogenetic protein gene therapy for the induction of spinal arthrodesis

1998 ◽  
Vol 4 (2) ◽  
pp. E14 ◽  
Author(s):  
Tord D. Alden ◽  
Gerald R. Hankins ◽  
Elisa J. Beres ◽  
David F. Kallmes ◽  
Gregory A. Helm
Keyword(s):  
Gene Therapy ◽  
Bone Formation ◽  
Spinal Fusion ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Lumbosacral Spine ◽  
Ct Reconstruction ◽  
Morphogenetic Protein ◽  
Adenoviral Construct

Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion. This study was undertaken to determine whether direct injection of an adenoviral construct containing the BMP-2 gene can be used for spinal fusion. Twelve athymic nude rats were used in this study. Recombinant, replication-defective type-5 adenovirus with a universal promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with a universal promoter and ß-galactosidase (ß-gal) gene (Ad-ß-gal) was used as a control. Seven and one-half microliters of virus was injected percutaneously and paraspinally at the lumbosacral junction in three groups (four animals each): 1) Ad-BMP-2 bilaterally, 2) Ad-BMP-2 on the right, Ad-ß-gal on the left, and 3) Ad-ß-gal bilaterally. Computerized tomography (CT) scans of the lumbosacral spine were obtained at 3, 5, and 12 weeks. At 12 weeks, the animals were killed for histological inspection. Ectopic bone formation was seen both on three-dimensional CT reconstruction and histologically in all rats at sites treated with Ad-BMP-2. Histological analysis revealed bone at different stages of maturity adjacent to the spinous processes, laminae, and transverse processes. This study clearly demonstrated that it is possible to produce in vivo endochondral bone formation by using direct adenoviral construct injection into the paraspinal musculature, which suggests that gene therapy may be useful for spinal fusion in the future.

The diameter of anodic TiO2 nanotubes affects bone formation and correlates with the bone morphogenetic protein-2 expression in vivo

2011 ◽  
Vol 23 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Cornelius von Wilmowsky ◽  
Sebastian Bauer ◽  
Stefanie Roedl ◽  
Friedrich Wilhelm Neukam ◽  
Patrik Schmuki ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Tio2 Nanotubes ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein

scholarly journals Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration

2020 ◽  
Vol 6 (1) ◽  
pp. eaay1240 ◽  
Author(s):  
Marian H. Hettiaratchi ◽  
Laxminarayanan Krishnan ◽  
Tel Rouse ◽  
Catherine Chou ◽  
Todd C. McDevitt ◽  
...  
Keyword(s):  
Bone Formation ◽  
Heterotopic Ossification ◽  
Bone Morphogenetic Protein ◽  
Spatial Localization ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Large Bone ◽  
Large Bone Defects

Supraphysiologic doses of bone morphogenetic protein-2 (BMP-2) are used clinically to promote bone formation in fracture nonunions, large bone defects, and spinal fusion. However, abnormal bone formation (i.e., heterotopic ossification) caused by rapid BMP-2 release from conventional collagen sponge scaffolds is a serious complication. We leveraged the strong affinity interactions between heparin microparticles (HMPs) and BMP-2 to improve protein delivery to bone defects. We first developed a computational model to investigate BMP-2–HMP interactions and demonstrated improved in vivo BMP-2 retention using HMPs. We then evaluated BMP-2–loaded HMPs as a treatment strategy for healing critically sized femoral defects in a rat model that displays heterotopic ossification with clinical BMP-2 doses (0.12 mg/kg body weight). HMPs increased BMP-2 retention in vivo, improving spatial localization of bone formation in large bone defects and reducing heterotopic ossification. Thus, HMPs provide a promising opportunity to improve the safety profile of scaffold-based BMP-2 delivery.

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