LncRNA H19 sponges miR-103-3p to promote the high phosphorus-induced osteoblast phenotypic transition of vascular smooth muscle cells by upregulating Runx2

Abstract

Elucidating the mechanism of the osteogenic phenotypic transdifferentiation of vascular smooth muscle cells (VSMCs) is the key to determining the diagnosis and treatment of arterial medial calcification (AMC). Long noncoding RNAs (lncRNAs) have been reported to participate in the regulation of vascular physiology and pathology. Here, we investigated the effect and mechanism of the lncRNA H19 on the osteoblastic differentiation of VSMCs induced by high phosphorus. H19 was expressed at high levels in high phosphorus-induced primary rat VSMCs. Further experiments indicated that H19 played a positive role in the osteoblast phenotypic transition by suppressing miR-103-3p expression and subsequently promoting osteoblast-specific marker expression, including bone morphogenetic protein 2 (BMP-2) and osteopontin (OPN). Mechanistically, we recognized RUNX family transcription factor 2 (Runx2) as a direct target of miR-103-3p. Moreover, H19 directly interacted with miR-103-3p, and overexpression of miR-103-3p reversed the upregulation of Runx2 induced by H19. Therefore, H19 positively regulated Runx2 expression by sponging miR-103-3p and promoted the osteoblast phenotypic transition in VSMC calcification. Collectively, the lncRNA H19 promoted osteogenic differentiation by modulating the miR-103-3p/Runx2 axis in the process of VSMC calcification induced by a high phosphorus concentration. The current study provided new insights into an important role for the lncRNA H19 as a miRNA sponge in VSMCs and supplied novel insights into lncRNA-directed diagnostics and therapeutics for vascular calcification.

Keywords: Competing endogenous RNAs; LncRNA H19; Osteoblast phenotypic transition; Runx2; miR-103-3p.