Promoting effect of long non-coding RNA SNHG1 on osteogenic differentiation of fibroblastic cells from the posterior longitudinal ligament by the microRNA-320b/IFNGR1 network

Abstract

ABSTRACT Long non-coding RNAs (lncRNAs) have been noted to influence the progression of ossification of posterior longitudinal ligament (OPLL). The work aims to probe the effect of lncRNA SNHG1 on osteogenic differentiation of ligament fibroblastic cells (LFCs). Aberrantly expressed lncRNAs in ossified PLL tissues were screened out by microarray analysis. Gain- and loss-of function experiments of SNHG1 were performed to identify its role in osteogenic differentiation of LFCs. The downstream molecules of SNHG1 were explored. Altered expression of miR-320b was introduced in LFCs as well. The interactions among SNHG1, miR-320b and IFNGR1 were identified. Consequently, SNHG1 was found highly expressed in OPLL patients. Silencing of SNHG1 inhibited BMP-2, RUNX2 and OCN expression and the ALP activity and reduced osteogenic differentiation of LFCs. Importantly, SNHG1 could and upregulate IFNGR1 through serving as a sponge for miR-320b. Over-expression of miR-320b inhibited osteogenic differentiation of LFCs and inactivated the JAK/STAT signaling pathway. Further administration of Fedratinib, a JAK2-specific agonist, increased osteogenic differentiation of LFCs. To conclude, the study suggested that SNHG1 could upregulate IFNGR1 by sequestering miR-320b and activate the JAK/STAT signaling. Silencing of SNHG1 could reduce the osteogenic differentiation and mineralization of LFCs. The study may offer new insights into OPLL treatment.