title: Controlled release of bone morphogenetic protein-2 enhances recruitment of osteogenic progenitor cells for de novo generation of bone tissue.
abstract: The objective of this study was to evaluate the cellular contribution to the phenomenon of de novo generation of bone tissue induced by the controlled release of bone morphogenetic protein-2 (BMP-2). Gelatin hydrogels (2 mg) incorporating BMP-2 (3 microg) with different water contents were subcutaneously implanted into the back of enhanced green fluorescent protein-chimeric mice to induce the ectopic de novo generation of bone tissue. The hydrogels incorporating BMP-2 could release BMP-2 at different time profiles. When evaluated radiologically and histologically, the ectopic de novo generation of bone tissue was induced by the controlled release of BMP-2 from the hydrogels around the hydrogel-implanted site. The relative percentage number of green fluorescent protein- to osteocalcin-positive cells recruited into the de novo generated bone tissue depended on the BMP-2 release profile. The higher the percentage, the stronger was the de novo generation of bone tissue. These findings indicate that bone marrow-derived osteoblast progenitor cells were recruited from the blood circulation by BMP-2 release and consequently contributed to the ectopic de novo generation of bone tissue. It is conceivable that the local concentration of BMP-2 modifies the recruitment profile of progenitor cells with an osteogenic potential around the release site of BMP-2, resulting in regulated volume of de novo generated bone tissue.
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University , Kyoto, Japan .
authors.forename: Yu
authors.initials: Y
authors.lastname: Kimura
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miyazaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Otsuru
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tamai
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000235:genetics; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005780:Gelatin; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020100:Hydrogels; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D004343:Drug Implants; D020100:Hydrogels; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D005780:Gelatin