TABLE 1.
Angiogenic Factors Involved in Dental Pulp Regeneration
| Type of element | Angiogenic effects | Mechanisms of action |
| DPSCs | Proangiogenic and antiangiogenic |
1. Expression of proangiogenic factors such as VEGF, FGF-2, PDGF, IGF-1, MMP-9, TGF-β, and MCP-1 |
| 2. Differentiation into endothelial-like cells | ||
| 3. Promoting endothelial cell migration by PI3K/AKT and MEK/ERK | ||
| Expression of antiangiogenic factors such as endostatin, IGFBP3, uPA, TIMP-1, and PAI-1 |
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| SHED | Proangiogenic | Differentiating into endothelial-like cells through the VEGF/MEK1/ERK signaling pathway |
| Dental pulp fibroblasts | Proangiogenic | Inducing the secretion of FGF-2 and VEGF |
| Orthodontic movements | Proangiogenic | Expression of proangiogenic factors such as VEGF, FGF-2, PDGF, EGF, and TGF-β |
| Dentin matrix components | Proangiogenic and antiangiogenic |
In low concentrations act as a reservoir of proangiogenic factors |
| In high concentrations act as antiangiogenic agent due to unknown mechanism | ||
| VEGF | Proangiogenic | 1. Proliferation and migration of endothelial cells and maturation of sprouted capillary vessels |
| 2. Activation of intrinsic tyrosine kinases | ||
| 3. Differentiation of DPSCs into endothelial cells | ||
| FGF (FGF-1 and FGF-2) | Proangiogenic | Proliferation and migration of endothelial cells |
| PDGF | Proangiogenic | Proliferation and migration of perivascular supporting cells |
| Angiopoietins (Ang-1 and Ang-2) |
Proangiogenic | Initiating and stabilization of angiogenesis through competitive interactions with Tie-2 receptor |
| MMP | Proangiogenic | Degradation of ECM of vessel walls allowing migration of endothelial cells |
| SCF | Proangiogenic | Homing or navigation of stem cells |
| Iloprost | Proangiogenic | Expression of VEGF, FGF-2, and PDGF |
| Simvastatin | Proangiogenic | 1. Enhancing the endothelial cell functions |
| 2. Stimulation of DPSCs to express odontogenic and angiogenic markers | ||
| Hinokitiol | Proangiogenic | Production of hypoxia-inducible factor-1alpha and VEGF in pulp cells |
| L-mimosine | Proangiogenic | Expression of VEGF |
| LL-37 peptide | Proangiogenic | Migration of human pulp cells |
| Metallothionein | Proangiogenic | Enhancement of angiogenesis events and proliferation of differentiated odontoblast cells |
| Hyperglycemia | Antiangiogenic | Interfering with immune system cells function and inhibiting cellular proliferation |