title: Insulin-like growth factor-1 (IGF-1) enhances the osteogenic activity of bone morphogenetic protein-6 (BMP-6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF-1 is combined with BMP-2.
abstract: Bone morphogenetic protein-2 (BMP-2) is widely used in orthopedic surgery and bone tissue engineering because of its strong osteogenic activity. However, BMP-2 treatments have several drawbacks and many groups are actively exploring alternatives. Since BMP-6 has been demonstrated to be more osteoinductive, its use, either alone or together with other growth factors, might be an interesting option. In this work, we have compared the effect of BMP-2, BMP-6, or insulin-like growth factor-1 (IGF-1), either alone or in combination. Murine preosteoblasts were treated with 15 nM IGF-1 and/or 6 nM BMP-2 or -6 and the expression of osteogenic marker genes, proliferation, and alkaline phosphatase (ALP) activity in vitro were analyzed. The results showed that IGF-1 greatly enhanced the BMP-induced osteogenic differentiation of these cells in general and that the ALP activity in the cultures was higher when the combination was made with BMP-6 than with BMP-2. Furthermore, we tested the osteogenic potential of these treatments in vivo by loading 25 pmoles of IGF-1 and/or 10 pmoles of BMP-2 or -6 onto absorbable collagen sponges and implanting them into an ectopic bone formation model in rats. This study revealed that only BMP-6 was able to induce bone formation at the used dose and that the addition of IGF-1 contributed to an increase of the mineralization in the implants. Hence, the combination of BMP-6 with IGF-1 might be a better alternative than BMP-2 for orthopedic surgery or bone tissue engineering approaches. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1867-1875, 2017.
authors.affiliation: Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, Malaga, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain.|BIONAND, Andalusian Center for Nanomedicine and Biotechnology (Junta de Andalucia, University of Malaga).
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Rico-Llanos
authors.affiliation: Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, Malaga, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain.|BIONAND, Andalusian Center for Nanomedicine and Biotechnology (Junta de Andalucia, University of Malaga).
authors.forename: Jose
authors.initials: J
authors.lastname: Becerra
authors.affiliation: Department of Cell Biology, Genetics and Physiology, University of Malaga, IBIMA, Malaga, Spain.|Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Malaga, Spain.|BIONAND, Andalusian Center for Nanomedicine and Biotechnology (Junta de Andalucia, University of Malaga).
authors.forename: Rick
authors.initials: R
authors.lastname: Visser
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology; D055418:Bone Morphogenetic Protein 6 / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; C525817:Bmp6 protein, mouse; C525818:Bmp6 protein, rat; D055396:Bone Morphogenetic Protein 2; D055418:Bone Morphogenetic Protein 6; C519530:insulin-like growth factor-1, mouse; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I
keywords: bone morphogenetic proteins (BMPs); bone tissue engineering; collagen; ectopic bone; insulin-like growth factor-1 (IGF-1); osteogenesis