title: Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration.
abstract: The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration.
authors.affiliation: Division of Oral Implantology, Department of Oral Rehabilitation, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.|Research Center for Regenerative Medicine, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Sato
authors.affiliation: Division of Cellular Physiology, Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.|Research Center for Regenerative Medicine, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiya
authors.affiliation: Division of Periodontology, Department of Odontology, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Mori
authors.affiliation: Division of Fixed Prosthodontics, Department of Oral Rehabilitation, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sato
authors.affiliation: Research Center for Regenerative Medicine, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Division of Oral Implantology, Department of Oral Rehabilitation, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kido
authors.affiliation: Research Center for Regenerative Medicine, Fukuoka Dental College, Tamura, Sawara-ku, Fukuoka, Japan.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0002-7790-1603
authors.initials: J
authors.lastname: Ohno
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000494:pharmacology*; D006801:Humans; D023421:Models, Animal; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D012474:Salmon / Q000235:genetics*
chemical_list: D004247:DNA; D000469:Alkaline Phosphatase