ABSTRACT
Background: Distraction osteogenesis (DO) is a widely used bone regenerative technique. However, the DO process is slow, and the consolidation phase is long. Therefore, it is of great clinical significance to explore the mechanism of DO, and shorten its duration. Recent studies reported that stem cell exosomes may play an important role in promoting angiogenesis related to DO, but the mechanism remains unclear. Methods: Canine endothelial colony-forming cells (ECFCs) were isolated and cultured, and the expression of THBS1 in canine ECFCs were inhibited using a lentiviral vector. The exosomes secreted by canine ECFCs were isolated and extracted, and the effect of exosomes on the angiogenic activity of Human umbilical vein endothelial cells (HUVECs) was detected by proliferation, migration, and tube formation experiments. WB and qRT-PCR were used to explore the effects and mechanisms of THBS1-mediated ECFC-Exos on HUVECs angiogenesis. Then, a mandibular distraction osteogenesis (MDO) model was established in adult male beagles, and exosomes were injected into the canine peripheral blood. Micro-CT, H&E, Masson, and IHC staining were used to explore the effects and mechanisms of THBS1-mediated ECFC-Exos on angiogenesis and osteogenesis in the DO area. Results: ECFC-Exo accelerated HUVECs proliferation, migration and tube formation, and this ability was enhanced by inhibiting the expression of THBS1 in ECFC-Exo. Using Western blot-mediated detection, we demonstrated that inhibiting THBS1 expression in ECFCs-Exo activated PI3K, AKT, and ERK phosphorylation levels in HUVECs, which promoted VEGF and bFGF expressions. In the DO model of the canine mandible, ECFCs-Exo injected into the peripheral blood aggregated into the DO gap, thus promoting angiogenesis and bone formation in the DO tissue by reducing THBS1 expression in ECFC-Exo. Conclusion: Our findings suggested that ECFC-Exos markedly enhances angiogenesis of endothelial cells, and promotes bone healing in canine MDO. Thus, THBS1 plays a crucial role in the ECFC-Exos-mediated regulation of canine MDO angiogenesis and bone remodeling. The translational potential of this article: This study reveals that the angiogenic promotion via THBS1 suppression in ECFC-Exos may be a promising strategy for shortening the DO duration.
ABSTRACT
In addition to its important transport functions, the skeletal system is involved in complex biological activities for the regulation of blood vessels. Endothelial progenitor cells (EPCs), as stem cells of endothelial cells (ECs), possess an effective proliferative capacity and a powerful angiogenic capacity prior to their differentiation. They demonstrate synergistic effects to promote bone regeneration and vascularization more effectively by co-culturing with multiple cells. EPCs demonstrate a significant therapeutic potential for the treatment of various bone diseases by secreting a combination of growth factors, regulating cellular functions, and promoting bone regeneration. In this review, we retrospect the definition and properties of EPCs, their interaction with mesenchymal stem cells, ECs, smooth muscle cells, and immune cells in bone regeneration, vascularization, and immunity, summarizing their mechanism of action and contribution to bone biology. Additionally, we generalized their role and potential mechanisms in the treatment of various bone diseases, possibly indicating their clinical application.
