LncRNA KCNQ1OT1 ameliorates particle-induced osteolysis through inducing macrophage polarization by inhibiting miR-21a-5p

Abstract

This study aimed to investigate the mechanism of lncRNA-KCNQ1OT1 on macrophage polarization to ameliorate particle-induced osteolysis. We used polymethylmethacrylate (PMMA) to induce primary bone marrow-derived macrophages (BMMs) obtained from mice and the RAW264.7 cell line, and found that the tumor necrosis factor-alpha (TNF-α) concentration and inducible nitric oxide synthase (iNOS) expression was increased, while interleukin (IL)-10 concentration and Arg1 expression were decreased in PMMA-induced cells. KCNQ1OT1 and IL-10 expression were both suppressed and miR-21a-5p expression was promoted in PMMA-induced cells. Overexpression of KCNQ1OT1 reversed the effect of PMMA on RAW264.7 cells, such as the reduced TNF-α concentration and iNOS expression, and increased IL-10 concentration and Arg1 expression in PMMA-induced cell transfected with pcDNA-KCNQ1OT1. The luciferase assay confirmed that IL-10 is a target of miR-21a-5p. RNA immunoprecipitation (RIP) and RNA pull-down experiments demonstrated that KCNQ1OT1 functions as a miR-21a-5p decoy. Thus, lncRNA KCNQ1OT1 induces M2 macrophage polarization to ameliorate particle-induced osteolysis by inhibiting miR-21a-5p.

Knockdown of lncRNA KCNQ1OT1 suppresses the adipogenic and osteogenic differentiation of tendon stem cell via downregulating miR-138 target genes PPARγ and RUNX2

“…Over the years, accumulating evidence exists with regard to the importance of lncRNA KCNQ1OT1in the development of musculoskeletal system. A recent study indicated that lncRNA KCNQ1OT1 ameliorated particle-induced osteolysis through inducing macrophage polarization by suppressing miR-21a-5p [21]. The present study showed that lncRNA KCNQ1OT1 was up-regulated in the injured tendon specimens of tendon injury mice model and during osteogenic and adipogenic differentiation of TSCs, which suggested that KCNQ1OT1 might involve in the osteogenic and adipogenic changes.…”

Long non‐coding RNA expressed in macrophage co‐varies with the inflammatory phenotype during macrophage development and polarization

“…82 KCNQ1OT1 could function as a miR-21a-5p decoy to up-regulate IL-10, induced polarization of macrophages into M2 type. 83,84 LncRNA TCONS_00019715 was expressed at a higher level when M2 macrophage was converted to M1, but decreased when M1 type was converted to M2 85…”

“…HOTTIP expression was associated with TLR tolerance, and has been speculated to skew macrophage polarization to a “M2‐like” phenotype . KCNQ1OT1 could function as a miR‐21a‐5p decoy to up‐regulate IL‐10, induced polarization of macrophages into M2 type . LncRNA TCONS_00019715 was expressed at a higher level when M2 macrophage was converted to M1, but decreased when M1 type was converted to M2…”

“…In polymethyl methacrylate (PMMA)‐induced BMDMs, the expression of TNF‐α, iNOS and miR‐21a‐5p were increased, but the expression of IL‐10, Arg1 and lncRNA KCNQ1OT1 were suppressed. KCNQ1OT1 might act as a miR‐21a‐5p decoy to up‐regulate IL‐10 expression, and then prompt macrophages into M2 type . A detailed transcriptome analysis in human macrophage revealed that lncRNA TCONS_00019715 was highly expressed when M2 type was converted to M1, but decreased when M1 type was converted to M2.…”

“…KCNQ1OT1 might act as a miR-21a-5p decoy to up-regulate IL-10 expression, 83 and then prompt macrophages into M2 type. 84 A detailed transcriptome analysis in human macrophage revealed that lncRNA TCONS_00019715 was highly expressed when M2 type was converted to M1, but decreased when M1 type was converted to M2. Like TCONS_00019715, overexpressed P21-activated kinase 1 (PAK1) in macrophage was helpful to M1 macrophage polarization.…”