Long noncoding RNAs: a missing link in osteoporosis

Silva, Andreia; Moura, Sara Reis; Teixeira, José H.; Barbosa, Mário A.; Santos, Susana G.; Almeida, Maria Inês

doi:10.1038/s41413-019-0048-9

Cited by 76 publications

(73 citation statements)

References 199 publications

(281 reference statements)

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“…The osteoblast differentiation is precisely controlled by a variety of intracellular signaling pathways. In recent years, emerging evidence has demonstrated that epigenetic pathways, including long noncoding RNAs (lncRNAs) [3], are playing critical roles in regulating osteoblast differentiation and thus considered as a new focus point in bone research.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Huai

et al. 2019

IJMS

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Osteoporosis, a disease characterized by both loss of bone mass and structural deterioration of bone, is the most common reason for a broken bone among the elderly. It is known that the attenuated differentiation ability of osteogenic cells has been regarded as one of the greatest contributors to age-related bone formation reduction. However, the effects of current therapies are still unsatisfactory. In this study we identify a novel long noncoding RNA AK045490 which is correlated with osteogenic differentiation and enriched in skeletal tissues of mice. In vitro analysis of bone-derived mesenchymal stem cells (BMSCs) showed that AK045490 inhibited osteoblast differentiation. In vivo inhibition of AK045490 by its small interfering RNA rescued bone formation in ovariectomized osteoporosis mice model. Mechanistically, AK045490 inhibited the nuclear translocation of β-catenin and downregulated the expression of TCF1, LEF1, and Runx2. The results suggest that Lnc-AK045490 suppresses β-catenin/TCF1/Runx2 signaling and inhibits osteoblast differentiation and bone formation, providing a novel mechanism of osteogenic differentiation and a potential drug target for osteoporosis.

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Section: Introductionmentioning

confidence: 99%

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

Chen

Huai

et al. 2019

IJMS

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“…Numerous studies have confirmed that lncRNAs participate in the initiation and progression of several types of bone diseases including bone tumors (27), osteoarthritis (OA) (28,29), osteoporosis (30,31), RA (32) and ankylosing spondylitis (AS) (33). MEG3 has been shown to be involved in the development of the all these bone diseases, as shown in Table II. MEG3 and bone tumors.…”

Section: Roles Of Lncrna Meg3 In Bone Diseasesmentioning

confidence: 95%

“…Recently, lncRNAs have emerged as novel regulatory markers of osteoporosis (30,31). Osteoporosis is a systemic skeletal disorder characterized by low bone mass, and is associated with an increase in the risk of bone fracture (59).…”

Section: Meg3 and Osteoporosismentioning

confidence: 99%

Long non‑coding RNA MEG3 is involved in osteogenic differentiation and bone diseases (Review)

Sun

Peng

et al. 2020

Biomed Rep

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Osteogenic differentiation originating from mesenchymal stem cells (MSCs) requires tight coordination of transcriptional factors, signaling pathways and biomechanical cues. Dysregulation of such reciprocal networks may influence the proliferation and apoptosis of MSCs and osteoblasts, thereby impairing bone metabolism and homeostasis. An increasing number of studies have shown that long non-coding (lnc)RNAs are involved in osteogenic differentiation and thus serve an important role in the initiation, development, and progression of bone diseases such as tumors, osteoarthritis and osteoporosis. It has been reported that the lncRNA, maternally expressed gene 3 (MEG3), regulates osteogenic differentiation of multiple MSCs and also acts as a critical mediator in the development of bone formation and associated diseases. In the present review, the proposed mechanisms underlying the roles of MEG3 in osteogenic differentiation and its potential effects on bone diseases are discussed. These discussions may help elucidate the roles of MEG3 in osteogenic differentiation and highlight potential biomarkers and therapeutic targets for the treatment of bone diseases. Contents 1. Introduction 2. Roles of lncRNA MEG3 in osteogenic differentiation 3. Roles of lncRNA MEG3 in bone diseases 4. Conclusion

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“…For these reasons, these lncRNAs were defined as competing endogenous RNAs (ceRNAs) ( Figure 1). lncRNAs have been associated with the development of osteoporosis, and some authors proposed their use as a diagnostic and therapeutic tool for osteoporosis [73][74][75][76][77][78]. For example, X-inactive-specific transcript (Xist) RNA has been described to inhibit osteogenic differentiation bone marrow mesenchymal stem cell [79].…”

Section: Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis

Muraca

Cappariello

2020

IJMS

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Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates that non-coding RNAs can be shuttled among the cells and tissues via EVs, allowing non-coding RNAs to reach distant cells and exert systemic effects. Resident bone cells, including osteoclasts, osteoblasts, osteocytes, and endothelial cells, are tightly regulated by non-coding RNAs, and many of them can be exported from the cells to neighboring ones through EVs, triggering pathological conditions. For these reasons, researchers have also started to exploit EVs as a theranostic tool to address osteoporosis. In this review, we summarize some recent findings regarding the EVs’ involvement in the fine regulation of non-coding RNAs in the context of bone metabolism and osteoporosis.

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Long noncoding RNAs: a missing link in osteoporosis

Cited by 76 publications

References 199 publications

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

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

Long non‑coding RNA MEG3 is involved in osteogenic differentiation and bone diseases (Review)

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis

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