LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells

• Published in: Cellular physiology and biochemistry Vol. 46; no. 1; pp. 401 - 417
• Main Authors: Quan, Hongyu, Liang, Mengmeng, Li, Nan, Dou, Ce, Liu, Chuan, Bai, Yun, Luo, Wei, Li, Jianmei, Kang, Fei, Cao, Zhen, Yang, Xiaochao, Jiang, Hong, Dong, Shiwu
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.04.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: AK131850; Angiogenesis; Animals; Base Sequence; Bone marrow; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Culture Media, Conditioned - pharmacology; Endothelial progenitor cells; Endothelial Progenitor Cells - cytology; Endothelial Progenitor Cells - metabolism; Gene expression; Kinases; Male; Mice; Mice, Inbred C57BL; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-93-5p; Newborn babies; Oligonucleotide Array Sequence Analysis; Original Paper; Osteoclast; Osteoclasts - cytology; Osteoclasts - metabolism; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; RNA Interference; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sequence Alignment; Signal transduction; Stem cells; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vasculogenesis; VEGFa; Osteoclast; MiR-93-5p; Vasculogenesis; AK131850; Endothelial progenitor cells; VEGFa
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000488474

Background/Aims: In the process of bone development and remodeling, the vasculature is regarded as the communicative network between the bone and neighboring tissues. Recently, it has been reported that the processes of angiogenesis and osteogenesis are coupled temporally and spatially. However, few studies reported the relationship and relevant mechanism between osteoclastogenesis and vasculogenesis. Methods: Arraystar Mouse lncRNA microarray V3.0 was firstly used to analyze the differentially expressed lncRNA genes in osteoclast different stages during osteoclastogenesis. Cell counting kit 8 (CCK-8) analysis, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, migration and tube formation assays were used to detect impact of osteoclast different stages on the proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs), respectively. Finally, transfection of AK131850 shRNA, miR-93-5p mimic and miR-93-5p inhibitor, qRT-PCR, western blotting, enzyme-linked immunosorbent assay (ELISA), fluorescence in situ hybridization (FISH) and luciferase reporter assay were carried out to dissect molecular mechanisms. Results: In this study, we found that newborn OCs (N-OC) and mature OCs (M-OC) during osteoclastogenesis significantly promoted proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs). Through lncRNA microarray and GO&pathway analysis, we found that AK131850 and co-expressed gene, vascular endothelial growth factor a (VEGFa), were significantly up-regulated in N-OC and M-OC. After inhibition of AK131850 the promoting effect of N-OC and M-OC on EPCs was reversed. Furthermore, we found that AK131850 directly competed miR-93-5p in N-OC and M-OC through sponge, thereby increasing VEGFa transcription, expression and secretion through derepressing of miR-93-5p on VEGFa. Conclusion: Our results provided the first finding that lncRNA-AK131850 sponged miR-93-5p in N-OC and M-OC during osteoclastogenesis to enhance the secretion of VEGFa, thus promoting vasculogenesis of EPCs.