Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells.
Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone morphogenetic proteins (BMPs) can regulate the differentiation of mesenchymal stem cells into cartilage, bone, tendon/ligament, and fat lineages. Early data documented the osteogenic potential of rhBMP2 and rhBMP7/OP-1. However, prior to this work that summarized several of our recent studies, no comprehensive analysis had been undertaken to characterize relative osteogenic activity of all BMPs. Using recombinant adenoviruses expressing 14 BMPs, we have demonstrated that, besides BMP2 and BMP7, BMP6 and BMP9 exhibit the highest osteogenic activity both in vitro and in vivo. We further demonstrated that several BMPs may exert synergistic effect on osteogenic differentiation, and that osteogenic BMPs produce a distinct set of molecular fingerprints during osteogenic differentiation. The reported work should expand our current understanding of BMP functions during osteogenic differentiation. It is conceivable that osteogenic BMPs (i.e., BMP2, 4, 6, 7, and 9) may be used to formulate synergistic pairs among themselves and/or with other less osteogenic BMPs for efficacious bone regeneration in clinical settings.
Luu
Hue H
HH
Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637, USA.
Song
Wen-Xin
WX
Luo
Xiaoji
X
Manning
David
D
Luo
Jinyong
J
Deng
Zhong-Liang
ZL
Sharff
Katie A
KA
Montag
Anthony G
AG
Haydon
Rex C
RC
He
Tong-Chuan
TC
D000818:Animals; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055398:Bone Morphogenetic Protein 3; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007273:Injections, Intramuscular; D007668:Kidney / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009999:Ossification, Heterotopic / Q000139:chemically induced / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525718:BMP2 protein, human; C525757:BMP3 protein, human; C525816:BMP6 protein, human; C525819:BMP7 protein, human; D015415:Biomarkers; C525719:Bmp2 protein, mouse; C525817:Bmp6 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055398:Bone Morphogenetic Protein 3; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C525887:GDF2 protein, human; C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta