Recombinant growth/differentiation factor-5 (GDF-5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic.
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.
Shimaoka
Hideki
H
Department of Public Health, Nara Medical University, 840 Shijocho, Kashihara, Nara 634-8521, Japan. hshmaoka@naramed-u.ac.jp
Dohi
Yoshiko
Y
Ohgushi
Hajime
H
Ikeuchi
Masako
M
Okamoto
Masanori
M
Kudo
Akira
A
Kirita
Tadaaki
T
Yonemasu
Kunio
K
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
D019485:Bone Morphogenetic Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017886:Durapatite