title: Combining bone morphogenetic proteins-2 and -6 has additive effects on osteoblastic differentiation in vitro and accelerates bone formation in vivo.
abstract: While only two members of the bone morphogenetic protein subfamily (BMP-2 and -7) are approved to be used in combination with collagen type I in orthopaedic surgery, other BMPs are known to also be highly osteoinductive. Although all the osteogenic BMPs signal through Smad-1/-5/-8 phosphorylation, they show different preferences for the available BMP receptors. In this work we studied the effect of combining two osteogenic BMPs (-2 and -6), which belong to different groups within the subfamily and have different affinities to the existing BMP receptors. Both the growth and in vitro differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells (MSCs) were studied, as well as in vivo ectopic bone formation when the BMPs were intramuscularly implanted in rats with collagen type I sponges as carriers. The results show that these two growth factors have additive effects on the osteoblastic differentiation of cells in vitro and that their combination might be helpful to accelerate in vivo osteogenesis while reducing the amount of each individual BMP used.
authors.affiliation: Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, BIONAND, Andalusian Center for Nanomedicine and Biotechnology, Malaga, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain.
authors.forename: Rick
authors.initials: R
authors.lastname: Visser
authors.affiliation: Department of Genetics, Faculty of Natural Sciences, Comenius University, Mlynska Dolina, 842 15 Bratislava, Slovakia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Bodnarova
authors.affiliation: Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, BIONAND, Andalusian Center for Nanomedicine and Biotechnology, Malaga, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain.
authors.forename: Pilar M
authors.initials: PM
authors.lastname: Arrabal
authors.affiliation: Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, BIONAND, Andalusian Center for Nanomedicine and Biotechnology, Malaga, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cifuentes
authors.affiliation: Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, BIONAND, Andalusian Center for Nanomedicine and Biotechnology, Malaga, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Becerra
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015151:Immunoblotting; D020007:Implants, Experimental; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011916:Rats, Inbred F344; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D055418:Bone Morphogenetic Protein 6; D051785:Smad Proteins; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: BMP (bone morphogenetic protein); collagen type I; ectopic bone; mesenchymal stem cell; osteogenesis