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Factor | Effect on osteogenesis | Effect on angiogenesis |
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BMP-2, BMP-4 | Activation of proliferation, differentiation, synthesis of components of bone intercellular matrix, and growth factors (VEGF, bFGF, etc.) [27, 28] Biological action is decreased by impact of BMP-3 [29]. | Influence on EPC. Stimulation of migration, proliferation, and formation of capillary-like structures; increase of VEGF and ANG-1 receptor expression; no effect on cell differentiation and survival [30, 31]. |
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BMP-3 | Suppression of differentiation; decrease of osteogenic activity [29]. | — |
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BMP-6 | Decrease of proliferative activity of MMSCs and activation of their differentiation [32] (to a greater extent than the other BMPs [33]). | Activation of EPC proliferation; organization of capillary-like structures [34]. |
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BMP-7 | Activation of proliferation, differentiation, and synthesis of components of bone intercellular matrix [35]. | Increase of endothelial cell proliferation, production of VEGF receptors, and induction of capillary-like structure formation [36]. |
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BMP-9 | Increase of bone intercellular matrix production without negative regulation by BMP-3 [37]. | Activation of endothelial cell proliferation, including production of angiogenic factor receptors (VEGF and ANG-1) [38]. |
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Vascular endothelial growth factor (VEGF) | Increase of proliferative activity, differentiation, and chemotaxis induction by gradient of concentration [39–42]. | Stimulation of proliferation, differentiation, migration, formation of capillary-like structures, and inhibition of endothelial cell apoptosis [43–45]. |
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Stromal-derived factor-1 (SDF-1) | Induction of cambial cell homing by concentration gradient and inhibition of differentiation [46]. | Activation of migration, proliferation, adhesion, and differentiation of EPCs [47]. |
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Angiopoietins 1 and 2 | — | Activation of differentiation; intercellular contact formation of endothelial cells in vessel wall (vascular stabilization) [48, 49]. |
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Erythropoietin | Stimulation of MMSC differentiation to osteoblasts and monocytes to osteoclasts, without increase of their activity [50]; increase of chondrocyte proliferation [51]. | Stimulation of endothelial cell proliferation [52] and NO production [53]. |
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Basic fibroblast growth factor | Increase of proliferation and suppression of differentiation [54]. | Increase of proliferation and suppression of EPC differentiation [55]. |
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Hepatocyte growth factor | activation of differentiation and synthesis of bone intercellular matrix components [56]. | Activation of proliferation and migration [57], inhibition of apoptosis, and decrease of endothelial permeability [58]. |
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Insulin-like growth factor-1 | Increase of mechanic sensitivity of specialized cells, induction of differentiation, and synthesis of bone intercellular matrix components in response to physical exercise [59]. | Activation of migration, proliferation and differentiation of endothelial cells, and induction of capillary-like structure formation [60]. |
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PDGF-AA | Insignificant increase of proliferation and differentiation; chemotaxis activation (to lesser extent than when exposed to PDGF-BB) [61]; increase of IGF-1 production. | — |
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PDGF-BB | Activation of cell proliferation and migration [62]. | Induction of pericyte migration, adhesion and incorporation to walls of forming vessels, and activation of EPC migration [63]. |
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TGF-β1 | Increase of proliferative activity, decrease of differentiation, and synthesis of bone intercellular matrix components [64]. | Activation, migration, proliferation, and formation of capillary-like structures [65]. |
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Angiogenin | — | Release of endothelial cells from vascular vessels and their activation and stimulation of migration and proliferation [66]. |
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