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

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

doi:10.3390/biomedicines8030065

Cited by 18 publications

(17 citation statements)

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“…Our study further confirms and extends this hypothesis demonstrating that the circulating GAS5 level is significantly increased in OP patients, specifically in subjects presenting fragility fractures. GAS5 expression level was found downregulated in hMSCs [ 24 ] and primary osteoblasts [ 9 ] from OP patients and its overexpression significantly induced ALP activity and promoted osteogenic differentiation of hMSCs through RUNX2 induction [ 24 ]. Moreover, Wang et al, by using an osteoporotic-induced mouse model, observed that GAS5 expression was increased during the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via negatively modulating miR-135a-5p to induce FOX1 expression [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…lncRNAs are important regulators of bone metabolism and changes in their expression pattern are linked to OP pathogenesis [ 7 , 8 ]. Recently, we demonstrated that lncRNAs involved in inflammatory responses are deregulated in cells from OP patients compared to controls [ 9 ]. Among them, the lncRNA growth arrest-specific transcript 5 (GAS5, MIM: #608280), encoded by the GAS5 gene at 1q25, has shown a five-fold downregulation of OP primary osteoblasts, thus indicating a possible role in OP [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we demonstrated that lncRNAs involved in inflammatory responses are deregulated in cells from OP patients compared to controls [ 9 ]. Among them, the lncRNA growth arrest-specific transcript 5 (GAS5, MIM: #608280), encoded by the GAS5 gene at 1q25, has shown a five-fold downregulation of OP primary osteoblasts, thus indicating a possible role in OP [ 9 ]. GAS5 has been widely studied in the field of cancer research where it acts as tumor suppressor by regulating cell cycle arrest and cell death [ 10 , 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Circulating Long Non-Coding RNA GAS5 Is Overexpressed in Serum from Osteoporotic Patients and Is Associated with Increased Risk of Bone Fragility

Visconti

Fittipaldi

Ciuffi

et al. 2020

IJMS

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Osteoporosis (OP) is a multifactorial disorder in which environmental factors along with genetic variants and epigenetic mechanisms have been implicated. Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of bone metabolism and OP aetiology. In this study, we analyzed the expression level and the genetic association of lncRNA GAS5 in OP patients compared to controls. Quantitative RT-PCR analysis of GAS5 was performed on the serum of 56 OP patients and 28 healthy individuals. OP subjects were divided into three groups of analysis: 29 with fragility fractures of lumbar spine (OP_VF), 14 with fragility fractures of femoral neck (OP_FF) and 13 without fractures (OP_WF). Genotyping of the rs145204276 insertion/deletion polymorphism has also been performed by Restriction fragment length polymorphism (RFLP) and direct sequencing analyses. Expression of circulating GAS5 is significantly increased in OP patients compared to controls (p < 0.01), with a statistically higher significance in fractured OP individuals vs. healthy subjects (p < 0.001). No statistically significant change was found in female OP patients; conversely, GAS5 is upregulated in the subgroup of fractured OP women sera (p < 0.01) and in all OP males (p < 0.05). Furthermore, a direct correlation between GAS5 expression level and parathyroid hormone (PTH) concentration was found in OP patients (r = 0.2930; p = 0.0389). Genetic analysis of rs145204276 revealed that the deletion allele was correlated with a higher expression of GAS5 in OP patients (0.22 ± 0.02 vs. 0.15 ± 0.01, ** p < 0.01). Our results suggest circulating GAS5 as a putative biomarker for the diagnosis and prognosis of OP and OP-related fractures.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating Long Non-Coding RNA GAS5 Is Overexpressed in Serum from Osteoporotic Patients and Is Associated with Increased Risk of Bone Fragility

Visconti

Fittipaldi

Ciuffi

et al. 2020

IJMS

Self Cite

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“…Selective estrogen receptor modulators (SERMs) act on estrogen receptors with agonist or antagonist activity, depending on the tissue type. Raloxifene (RLX) is an SERM used for the treatment of postmenopausal osteoporosis (OP) because of its activity as an estrogen receptor agonist in bone [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The effect of RLX can be tissue- or species-specific [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

Cheng

Chang

et al. 2021

Biomedicines

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Osteoarthritis (OA) and osteoporosis (OP) are common among older women, especially postmenopausal women. Glucosamine (GlcN) is a common medication for OA, but it may induce insulin resistance and β-cell dysfunction, especially if ovarian hormones are lacking. Raloxifene (RLX) is a selective estrogen receptor modulator and also an OP drug. Previously, we found that estrogen could improve GlcN-induced insulin resistance in ovariectomized (OVX) rats. Here, we further hypothesized that RLX, similarly to estrogen, can ameliorate GlcN-induced insulin resistance in OVX rats. We used GlcN to induce insulin resistance in OVX rats as a model for evaluating the protective effects of RLX in vivo. We used a pancreatic β-cell line, MIN-6, to study the mechanisms underlying the effect of RLX in GlcN-induced β-cell dysfunction in vitro. Increases in fasting plasma glucose, insulin, and homeostasis model assessments of insulin resistance in OVX Sprague Dawley rats treated with GlcN were reversed by RLX treatment (n = 8 in each group). Skeletal muscle GLUT-4 increased, liver PEPCK decreased, pancreatic islet hypertrophy, and β-cell apoptosis in OVX rats treated with GlcN was ameliorated by RLX. The negative effects of GlcN on insulin secretion and cell viability in MIN-6 cells were related to the upregulation of reticulum (ER) stress-associated proteins (C/EBP homologous protein, phospho-extracellular signal-regulated kinase, phospho-c-JunN-terminal kinase), the expression of which was reduced by RLX. Pretreatment with estrogen receptor antagonists reversed the protective effects of RLX. GlcN can induce insulin resistance, β-cell dysfunction, and apoptosis in OVX rats and increase ER stress-related proteins in β-cells, whereas RLX can reverse these adverse effects. The effects of RLX act mainly through estrogen receptor α; therefore, RLX may be a candidate drug for postmenopausal women with OA and OP.

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“…A number of lncRNAs have been shown to interact with miRNAs during osteoblast differentiation [97]. H19/miR-675 was reported to suppress mRNA and protein expression of transforming growth factor-β1 (TGF-β1) and histone deacetylase (HDAC) 4/5.…”

Section: Interactions Between Lncrnas and Mirnasmentioning

confidence: 99%

The roles of miRNA, lncRNA and circRNA in the development of osteoporosis

et al. 2020

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Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

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

Cited by 18 publications

References 50 publications

Circulating Long Non-Coding RNA GAS5 Is Overexpressed in Serum from Osteoporotic Patients and Is Associated with Increased Risk of Bone Fragility

Circulating Long Non-Coding RNA GAS5 Is Overexpressed in Serum from Osteoporotic Patients and Is Associated with Increased Risk of Bone Fragility

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

The roles of miRNA, lncRNA and circRNA in the development of osteoporosis

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