Osteogenic protein-1, a bone morphogenic protein member of the TGF-beta superfamily, shares chemotactic but not fibrogenic properties with TGF-beta.
We have previously shown that recombinant human osteogenic protein-1 (rhOP-1), a bone morphogenetic protein member of the TGF-beta superfamily, can induce new bone formation when implanted with an appropriate carrier at subcutaneous sites in rats and can restore completely large diaphyseal segmental defects in laboratory animals. The role of OP-1 in the early events of bone induction viz, chemotaxis of phagocytic leukocytes, and fibroblastic mesenchymal cells is currently unknown. In the present study, we examined the effect of rhOP-1 on chemotaxis of phagocytic leukocytes (human neutrophils and monocytes) and fibroblastic mesenchymal cells (infant foreskin fibroblasts). Since OP-1 is structurally related to TGF-beta 1, we assessed the effects of OP-1 on several other fibroblast functions (in addition to chemotaxis) known to be modulated by TGF-beta 1. Our results demonstrated that rhOP-1, like TGF-beta 1, is a potent chemoattractant for human neutrophils, monocytes, and fibroblasts. However, in contrast to TGF-beta 1, OP-1 does not to stimulate fibroblast mitogenesis, matrix synthesis [collagen and hyaluronic acid (hyaluronan)], or production of tissue inhibitor of metalloproteinase (TIMP), i.e., fibroblast functions associated with fibrogenesis. These results clearly demonstrate a dichotomy between these two members of the TGF-beta superfamily with a regard to fibrogenic effects on fibroblasts but a similarity in their chemotactic properties.
Postlethwaite
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AE
Department of Medicine, University of Tennessee, Memphis 38163.
Raghow
R
R
Stricklin
G
G
Ballou
L
L
Sampath
T K
TK
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002630:Chemotactic Factors; D006023:Glycoproteins; D011506:Proteins; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D006820:Hyaluronic Acid; D003094:Collagen; D015232:Dinoprostone