Identification of Aberrantly-Expressed Long Non-Coding RNAs in Osteoblastic Cells from Osteoporotic Patients

Federica Centofanti, Massimo Santoro, Mario Marini, Virginia Veronica Visconti, Anna Maria Rinaldi, Monica Celi, Giovanna D'Arcangelo, Giuseppe Novelli, Augusto Orlandi, Virginia Tancredi, Umberto Tarantino, Annalisa Botta

Research output: Contribution to journalArticle

Abstract

Osteoporosis (OP) is a multifactorial disease influenced by genetic, epigenetic, and environmental factors. One of the main causes of the bone homeostasis alteration is inflammation resulting in excessive bone resorption. Long non-coding RNAs (lncRNAs), have a crucial role in regulating many important biological processes in bone, including inflammation. We designed our study to identify lncRNAs misregulated in osteoblast primary cultures derived from OP patients (n = 4), and controls (CTRs, n = 4) with the aim of predicting possible RNA and/or protein targets implicated in this multifactorial disease. We focused on 84 lncRNAs regulating the expression of pro-inflammatory and anti-inflammatory genes and miRNAs. In silico analysis was utilized to predict the interaction of lncRNAs with miRNAs, mRNAs, and proteins targets. Six lncRNAs were significantly down-regulated in OP patients compared to controls: CEP83-AS1, RP11-84C13.1, CTC-487M23.5, GAS5, NCBP2-AS2, and SDCBP2-AS1. Bioinformatic analyses identified HDCA2, PTX3, and FGF2 proteins as downstream targets of CTC-487M23.5, GAS5, and RP11-84C13.1 lncRNAs mediated by the interaction with miRNAs implicated in OP pathogenesis, including miR-21-5p. Altogether, these data open a new regulatory mechanism of gene expression in bone homeostasis and could direct the development of future therapeutic approaches.

Original languageEnglish
JournalBiomedicines
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 19 2020

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    Centofanti, F., Santoro, M., Marini, M., Visconti, V. V., Rinaldi, A. M., Celi, M., D'Arcangelo, G., Novelli, G., Orlandi, A., Tancredi, V., Tarantino, U., & Botta, A. (2020). Identification of Aberrantly-Expressed Long Non-Coding RNAs in Osteoblastic Cells from Osteoporotic Patients. Biomedicines, 8(3). https://doi.org/10.3390/biomedicines8030065