title: Recombinant growth/differentiation factor-5 (GDF-5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic.
abstract: To evaluate the growth/differentiation factor-5 (GDF-5) in the in vivo osteogenic potential of bone marrow mesenchymal stem cells (MSCs), we subcutaneously implanted five different kinds of hydroxyapatite (HA) ceramic implants: HA alone, GDF-5/HA composites (GDF/HA), MSCs/HA composites, the MSCs/HA composites supplemented with GDF-5 (GDF/MSCs/HA), and recombinant bone morphogenetic protein-2 (BMP/MSCs/HA). Neither the HA alone nor the GDF/HA composites exhibited any bone formation at any time after implantation. At 4 weeks, the MSCs/HA composites exhibited a certain amount of bone formation in some pore areas. In contrast, at 2 weeks, the GDF/MSCs/HA composites exhibited histologically obvious de novo bone formation together with active osteoblasts in many pore areas and additional bone formation at 4 weeks. In the de novo formed bone, neither chondrocytes nor endochondral bone was detected. The GDF/MSCs/HA composites also showed high alkaline phosphatase (ALP) and osteocalcin expression determined at both the protein and gene levels and the high level of expression was well maintained even at 4 weeks. Compared with GDF/MSCs/HA, the BMP/MSCs/HA composites exhibited excellent osteogenesis with relatively early osteoblastic phenotype expression. The results indicate that GDF-5 synergistically enhances de novo bone formation capability of MSCs/HA composite and suggest that tissue-engineered GDF/MSCs/HA composites could be used as bone graft substitutes.
authors.affiliation: Department of Public Health, Nara Medical University, 840 Shijocho, Kashihara, Nara 634-8521, Japan. hshmaoka@naramed-u.ac.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Shimaoka
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Dohi
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohgushi
authors.forename: Masako
authors.initials: M
authors.lastname: Ikeuchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Okamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.forename: Kunio
authors.initials: K
authors.lastname: Yonemasu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002516:Ceramics; D017886:Durapatite; D055428:Growth Differentiation Factor 5; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D008297:Male; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D019485:Bone Morphogenetic Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017886:Durapatite