A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation

Abstract

The incidence of postmenopausal osteoporosis research 50% in middle‐aged and older women, however, effects of existing therapy are not ideal. Emerging evidence have proved that long noncoding RNAs (lncRNAs) was correlated with multiple physiological and pathology processes including development, carcinogenesis, and osteogenesis. However, reports on lncRNAs regulating bone formation were relatively limited. In this study, we screened osteogenic lncRNAs through mRNA/lncRNA microarray combined with gene coexpression analysis. The biological function of the screened lncRNA was assessed both in vitro and in vivo. The effects of the lncRNA on osteogenic transcription factors were also evaluated. We identified AK016739, which was correlated with osteogenic differentiation and enriched in skeletal tissues of mice. The expression levels of AK016739 in bone‐derived mesenchymal stem cells were increased with age and negatively correlated with osteogenic differentiation marker genes. Experiments showed that AK016739 inhibited osteoblast differentiation, and in vivo inhibition of AK016739 by its small interfering RNA would rescue bone formation in ovariectomized osteoporosis mice model. In addition, AK016739 suppressed both expression levels and activities of osteogenic transcription factors. This newly identified lncRNA AK016739 has revealed a new mechanism of osteogenic differentiation and provided new targets for treatment of skeletal disorders.

Silencing of lncRNA AK045490 Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis

“…Using human whole transcriptome microarray, Zhang et al profiled the expression and analyzed the functional network of lncRNAs during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSC), in which a total of 1408 lncRNAs with 623 lncRNAs downregulating and 785 lncRNAs significantly upregulating were detected along with osteogenic differentiation [12]. In this study, we screened osteogenic-related lncRNAs in our established preosteoblast cell line [13] by performing mRNA and lncRNA microarray in combination with KEGG analysis and PCC co-expression analysis [7]. Among them, AK045490 was one of lncRNAs that showed the most significant increment [7].…”

“…In our previous study, we have screened osteogenic lncRNAs through mRNA/lncRNA microarray combined with gene co-expression analysis. We speculate that AK045490 might be one of the osteoblastic differentiation inhibiting lncRNAs [7]. To determine the expression level of AK045490, we established two osteoporotic mice models, age-related osteoporotic mice model (aging mice) and postmenopausal osteoporotic mice model (ovariectomized mice, OVX mice).…”

“…Several lncRNAs have been identified to be essential in regulating osteoblastic differentiation of stem cells [5,6]. For example, LncRNA AK045490 inhibits osteoblast differentiation and bone formation by regulating transcription factor T cell factor 1(TCF1)/lymphoid enhancer-binding factor 1(LEF1) activity in mouse mesenchymal stem cells (mMSCs) [7]. Linc-ROR promotes osteogenic differentiation of human bone-marrow-derived mesenchymal stem cells (hMSCs) via activating Wnt/β-catenin pathway [8].…”

Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo

“…An increasing number of experiments have confirmed that lncRNAs can regulate osteoblast functions, such as differentiation and apoptosis 18,23,26,33 . Our previous research first identified a sensitive lncRNA, lncRNA ODSM, in osteoblasts in a MG unloading environment that could promote osteoblast differentiation 27 .…”

“…Recent studies have indicated that lncRNAs are associated with osteoporosis and other bone diseases 17 . Inhibiting AK016739 expression in vivo promoted osteogenic gene expression and rescued calvarial bone formation in ovariectomy (OVX) mice 18 . LncRNAs are involved in osteoblast differentiation and apoptosis.…”