Differences in the fusion and resorption activity of human osteoclasts after stimulation with different growth factors released from a polylactide carrier.
Previous in vivo studies were able to demonstrate the efficacy of locally released growth factors IGF-I, TGF-beta1, and BMP-2 from a poly(D,L-lactide) (PDLLA) implant coating on fracture healing. In vitro studies using human osteoblast-like cells showed an enhanced collagen-1 production due to growth factor application without an effect of the PDLLA on the investigated parameter. Both bone-forming osteoblasts and bone-resorbing osteoclasts are important during bone formation and fracture healing. The aim of this study was to investigate the influence of different growth factors and the polylactide coating into which they were incorporated on isolated osteoclasts. In vitro studies using human osteoclast-like cells derived from peripheral blood mononuclear cells (PBMNCs) were performed. Titanium K-wires coated with the lactide loaded with IGF-I and TGF-beta1 (alone and in combination) or BMP-2 were added to the culture in a non-contact manner and the fusion, resorption activity (pit formation assay), and TRAP 5b synthesis of the cells were analyzed. Differences in the effect of the growth factors were seen depending on the differentiation state of the cells. The fusion of the monocytes to multinuclear osteoclasts was significantly enhanced by the application of TGF-beta1 both alone and in combination with IGF-I. No effect was seen after application of IGF-I alone or BMP-2. The resorption activity of the osteoclasts analyzed on dentine chips was significantly enhanced after application of TGF-beta1 or BMP-2. These results indicate a differentiation-dependent effect of growth factors on osteoclasts. TGF-beta1 affects both the osteoclastogenesis and the activity of osteoclasts, whereas BMP-2 had an effect only on the activity of mature osteoclasts but not on the fusion of the PBMNCs.
Center for Musculoskeletal Surgery, Charité, Campus Virchow, University Medicine, Augustenburger Platz1, D-13353, Berlin, Germany. britt.wildemann@charite.de
B
B
Wildemann
A
A
Kadow-Romacker
M
M
Lübberstedt
M
M
Raschke
N P
NP
Haas
G
G
Schmidmaier
D000135:Acid Phosphatase / Q000096:biosynthesis; D000328:Adult; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D001862:Bone Resorption / Q000139:chemically induced*; D002459:Cell Fusion; D002478:Cells, Cultured; D004337:Drug Carriers; D004338:Drug Combinations; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011091:Polyesters; D000071681:Tartrate-Resistant Acid Phosphatase; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D004338:Drug Combinations; D006133:Growth Substances; D007527:Isoenzymes; D011091:Polyesters; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase