BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells.
For bone development, remodeling, and repair; the recruitment of mesenchymal progenitor cells (MPC) and their differentiation to osteoblasts is mandatory. The process of migration is believed to be regulated in part by growth factors stored within the bone matrix and released by bone resorption. In this study, primary human MPCs and to osteoblasts differentiated progenitor cells were examined for chemotaxis in response to human basic fibroblast growth factor (rhbFGF), human transforming growth factor beta 1 (rhTGF-beta1), human platelet derived growth factor bb (rhPDGF-bb), human bone morphogenetic protein-2 (rhBMP-2), and recombinant bone morphogenetic protein-4 of Xenopus laevis (rxBMP-4) from 0.001 to 1.0 ng/ml each. The results of migration were expressed as a chemotactic index (CI). Migration of primary human progenitor cells was stimulated by rhBMP-2, rxBMP-4, and rhPDGF-bb in a dose-dependent manner. The increase of CI was up to 3.5-fold for rhBMP-2, 3.6-fold for rxBMP-4, and up to 22-fold for rhPDGF-bb, whereas rhTGF-beta1 and rhbFGF did not stimulate cell migration in the concentration range tested. In contrast differentiated progenitor cells behave similar to primary human osteoblasts. RhBMP-2, rhPDGF-bb, and rhTGF-beta1 stimulated the migration from 2.2 to 2.4-fold each, while rxBMP-4 and rhbFGF reached only a CI of 1.7-1.6. The effect of rhBMP-2, rxBMP-4, and rhPDGF-bb as chemoattractive proteins for primary human MPC, including the change in response to growth factors after differentiation suggests a functional role for recruitment of MPCs during bone development and remodeling, as well as fracture healing.
Fiedler
Jörg
J
Division for Biochemistry of Joint and Connective Tissue Diseases, University of Ulm, Germany.
Röderer
Götz
G
Günther
Klaus-Peter
KP
Brenner
Rolf E
RE
D000077214:Becaplermin; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology; D029867:Xenopus Proteins
C525718:BMP2 protein, human; C525809:BMP4 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C499469:recombinant human bone morphogenetic protein-2; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin