Growth differentiation factor 15 promotes blood vessel growth by stimulating cell cycle progression in repair of critical-sized calvarial defect

Abstract

Repair of large bone defects remains a challenge for surgeons, tissue engineering represents a promising approach. However, the use of this technique is limited by delayed vascularization in central regions of the scaffold. Growth differentiation factor 15(GDF15) has recently been reported to be a potential angiogenic cytokine and has an ability to promote the proliferation of human umbilical vein endothelial cells(HUVECs). Whether it can be applied for promoting vascularized bone regeneration is still unknown. In this study, we demonstrated that GDF15 augmented the expression of cyclins D1 and E, induced Rb phosphorylation and E2F-1 nuclear translocation, as well as increased HUVECs proliferation. Furthermore, we also observed that GDF15 promoted the formation of functional vessels at an artificially-induced angiogenic site, and remarkably improved the healing in the repair of critical-sized calvarial defects. Our results confirm the essential role of GDF15 in angiogenesis and suggest its potential beneficial use in regenerative medicine.

Visfatin Mediates Malignant Behaviors through Adipose-Derived Stem Cells Intermediary in Breast Cancer

“…This was reversed with GDF15 neutralizing antibody and wortmannin inhibitor. Although GDF15 has been reported by others to promote angiogenesis in tube formation assays with HUVEC cells [45], we found that treatment with GDF15 neutralizing antibody did not inhibit the angiogenic effect from vADSCs. This implied that a GDF15 independent pathway may be involved in vADSCs related angiogenesis.…”

Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells

“…Remarkably, by using GO analysis, we found that several of these E2F1 targets encode for regulators of angiogenesis and/or vascular development, as exemplified in Supplementary Figure S7B. In line with our observation, several works described the pivotal role of E2F1 in vascular biology [68][69][70][71][72]. Accordingly, E2F1 binding sites are present in several genes encoding for factors involved in angiogenesis (such as FLT-1, KDR, and Angiopoietin 2), and E2F1 binding to these promoters is induced in ECs upon VEGF stimulation [72].…”

Prediction of Cardiovascular Clinical Outcomes with Novel Biomarker: the Focus on Growth Differentiation Factor 15

“…Probably, GDF-15 could be a central autocrine/paracrine factor that plays a pivotal role in intercellular communication within the myocardium aimed preventing stress-induced, ischemia-induced and inflammatory-related cardiac diseases. The essential role of GDF-15 in neovascularization and angiogenesis was confirmed in animal investigations and regarded an ability of the cytokine to promote the proliferation of human umbilical vein endothelial cells and remarkably improved vascular reparation [20]. In fact, GDF-15 acting as an angiogenic cytokine promoted tissue reparation in the healing and injury.…”