VCAM-1 Promotes Angiogenesis of Bone Marrow Mesenchymal Stem Cells Derived from Patients with Trauma-Induced Osteonecrosis of the Femoral Head by Regulating the Apelin/CCN2 Pathway

Yiming Shao; Lei Sun; Baodong Ma; Ranran Jin; Yueyao Ban; Ruibo Li; Jianfa Wang; Hongkai Lian; Han Yue

doi:10.1155/2023/6684617

VCAM-1 Promotes Angiogenesis of Bone Marrow Mesenchymal Stem Cells Derived from Patients with Trauma-Induced Osteonecrosis of the Femoral Head by Regulating the Apelin/CCN2 Pathway

Stem Cells Int. 2023 Oct 12:2023:6684617. doi: 10.1155/2023/6684617. eCollection 2023.

Authors

Yiming Shao^{1

2

3}, Lei Sun², Baodong Ma², Ranran Jin², Yueyao Ban³, Ruibo Li³, Jianfa Wang¹, Hongkai Lian¹, Han Yue²

Affiliations

¹ Department of Orthopedics, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450001, China.
² Center of Stem Cell and Regenerative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450001, China.
³ Department of Trauma Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450001, China.

Abstract

Trauma-induced osteonecrosis of the femoral head (TI-ONFH) is a pathological process in which the destruction of blood vessels supplying blood to the femoral head causes the death of bone tissue cells. Vascular cell adhesion molecule 1 (VCAM-1) has been shown to have potent proangiogenic activity, but the role in angiogenesis of TI-ONFH is unclear. In this work, we discovered that VCAM-1 was significantly downregulated in the bone marrow mesenchymal stem cells (BMSCs) derived from patients with TI-ONFH. Subsequently, we constructed BMSCs overexpressing VCAM-1 using a lentiviral vector. VCAM-1 enhances the migration and angiogenesis of BMSCs. We further performed mRNA transcriptome sequencing to explore the mechanisms by which VCAM-1 promotes angiogenesis. Gene ontology biological process enrichment analysis demonstrated that upregulated differentially expressed genes (DEGs) were related to blood vessel development. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that upregulated DEGs were engaged in the Apelin signaling pathway. Apelin-13 is the endogenous ligand of the APJ receptor and activates this G protein-coupled receptor. Treatment with Apelin-13 activated the Apelin signaling pathway and suppressed the expression of cellular communication network factor 2 in BMSCs. Furthermore, Apelin-13 also inhibits the migration and angiogenesis of VCAM-1-BMSCs. In summary, VCAM-1 plays an important role in vascular microcirculation disorders of TI-ONFH, which provides a new direction for the molecular mechanism and treatment of TI-ONFH.