TY - JOUR
T1 - Identification of aberrantly-expressed long non-coding rnas in osteoblastic cells from osteoporotic patients
AU - Centofanti, Federica
AU - Santoro, Massimo
AU - Marini, Mario
AU - Visconti, Virginia Veronica
AU - Rinaldi, Anna Maria
AU - Celi, Monica
AU - D'Arcangelo, Giovanna
AU - Novelli, Giuseppe
AU - Orlandi, Augusto
AU - Tancredi, Virginia
AU - Tarantino, Umberto
AU - Botta, Annalisa
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - Bone homeostasis
KW - Epigenetics
KW - Inflammation
KW - Long non-coding RNAs
KW - Osteoblast
KW - Osteoporosis
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U2 - 10.3390/biomedicines8030065
DO - 10.3390/biomedicines8030065
M3 - Article
AN - SCOPUS:85083716439
VL - 8
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 3
M1 - 65
ER -