Synergistic effects of the dual release of stromal cell-derived factor-1 and bone morphogenetic protein-2 from hydrogels on bone regeneration.
The objective of this study is to evaluate the activity of gelatin hydrogels incorporating combined stromal cell-derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2) on the in vivo bone regeneration at an ulna critical-sized defect and subcutaneous site of rats, and compared with that of those incorporating either SDF-1 or BMP-2. The similar release profile of SDF-1 and BMP-2 from the hydrogels was observed with or without the combination of BMP-2 and SDF-1, respectively. An enhanced bone regeneration by the hydrogels incorporating combined SDF-1 and BMP-2 was observed. In addition, the implantation of hydrogels incorporating combined SDF-1 and BMP-2 enhanced the expression level of CXC chemokine cell-surface receptor-4 (Cxcr4), Runt-related factor-2 (Runx2), and Osteocalcin genes. The experiments with green fluorescent protein (GFP)-positive Chimeric mice revealed that the recruitment of bone marrow-derived cells was promoted and a vascular-like structure together with strong accumulation of CD31- and CD34-positive cells was observed at the site of hydrogels incorporating combined SDF-1 and BMP-2 implanted. In addition, a large fraction of CD29- and CD44-positive non-hematopoietic cells was detected. It is concluded that the combined release of SDF-1 and BMP-2 enhanced the recruitment of osteogenic cells and angiogenesis, resulting in the synergistic effect on bone regeneration.
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Juthamas
J
Ratanavaraporn
Hiroyuki
H
Furuya
Hiroshi
H
Kohara
Yasuhiko
Y
Tabata
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000494:pharmacology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005780:Gelatin / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods; D055114:X-Ray Microtomography
D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D050659:Core Binding Factor Alpha 1 Subunit; D020100:Hydrogels; D019718:Receptors, CXCR4; D015675:Osteocalcin; D005780:Gelatin