Pulsed electromagnetic fields enhance BMP-2 dependent osteoblastic differentiation of human mesenchymal stem cells.
Mesenchymal stem cells (MSCs) express an osteoblastic phenotype when treated with BMP-2, and BMP-2 is used clinically to induce bone formation although high doses are required. Pulsed electromagnetic fields (PEMF) also promote osteogenesis in vivo, in part through direct action on osteoblasts. We tested the hypothesis that PEMF enhances osteogenesis of MSCs in the presence of an inductive stimulus like BMP-2. Confluent cultures of human MSCs were grown on calcium phosphate disks and were treated with osteogenic media (OM), OM containing 40 ng/mL rhBMP-2, OM + PEMF (8 h/day), or OM + BMP-2 + PEMF. MSCs demonstrated minor increases in alkaline phosphatase (ALP) during 24 days in culture and no change in osteocalcin. OM increased ALP and osteocalcin by day 6, but PEMF had no additional effect at any time. BMP-2 was stimulatory over OM, and PEMF + BMP-2 synergistically increased ALP and osteocalcin. PEMF also enhanced the effects of BMP-2 on PGE2, latent and active TGF-beta1, and osteoprotegerin. Effects of PEMF on BMP-2-treated cells were greatest at days 12 to 20. These results demonstrate that PEMF enhances osteogenic effects of BMP-2 on MSCs cultured on calcium phosphate substrates, suggesting that PEMF will improve MSC response to BMP-2 in vivo in a bone environment.
Schwartz
Z
Z
Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, Georgia 30332, USA.
Simon
B J
BJ
Duran
M A
MA
Barabino
G
G
Chaudhri
R
R
Boyan
B D
BD
D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D004574:Electromagnetic Fields; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D053244:Osteoprotegerin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D053244:Osteoprotegerin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D015232:Dinoprostone