Synergistic induction of early stage of bone formation by combination of recombinant human bone morphogenetic protein-2 and epidermal growth factor.
This study evaluates whether the combination of the rhBMP-2 and various types of growth factors including EGF, FGF, PDGF and VEGF increases osteoinductivity compared to the single use of rhBMP-2 through in vitro and in vivo study. Cultured human MSCs were treated with rhBMP-2 only or in combination with growth factors. For in vivo evaluation, rhBMP-2 only or with growth factors was implanted into the calvarial defect made on SD rats. Both EGF and PDGF significantly increased both ALP activity and expression level in hMSCs when treated in combination with rhBMP-2 at 3 and 7 days of differentiation and significantly raised the accumulation of the calcium at day 14. Furthermore, micro-CT scanning revealed that the EGF an FGF groups show significantly increased new bone surface ratio compared to the rhBMP-2 only group and, the EGF treatment significantly up regulated percent bone volume and trabecular number at two weeks after the surgery. VEGF treatment also significantly raised trabecular number and FGF treatment significantly increased the trabecular thickness. Histological examination revealed that the EGF combination group showed enhanced bone regeneration than the rhBMP-2 only group two weeks after the implantation. Even though the treatment of rhBMP-2 with PDGF and FGF failed to show enhanced osteogenesis in vitro and in vivo simultaneously, these results suggest that the positive effect of the combination of EGF and rhBMP-2 is expected to induce the bone formation earlier compared to the single use of rhBMP-2 in vitro and in vivo.
Department of Orthopaedic Surgery, College of Medicine, Seoul National University, Korea; Institute of Medical and Biological Engineering, Medical Research Centre, Seoul National University, Korea; SMG-SNU Boramae Medical Centre, Seoul, Korea.
Jae Hyup
JH
Lee
Soo-Jeong
SJ
Jang
Hae-Ri
HR
Baek
Kyung Mee
KM
Lee
Bong-Soon
BS
Chang
Choon-Ki
CK
Lee
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D050723:Fractures, Bone / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor
bone formation; calvarial defect model; epidermal growth factor; osteoblastic differentiation; rhBMP-2; synergistic effect