Overexpression of DNMT1 leads to hypermethylation of H19 promoter and inhibition of Erk signaling pathway in disuse osteoporosis

Li, Bing; Zhao, Jie; Ma, Jianxiong; Li, Guomin; Zhang, Yang; Xing, Guosheng; Li, Jun; Ma, Xiaofang

doi:10.1016/j.bone.2018.03.017

Cited by 53 publications

(61 citation statements)

References 30 publications

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“…[24][25][26][27] Importantly, although the roles of lncRNAs in the process of osteogenesis have been widely reported, [28][29][30] only a few studies have shown that lncRNAs are involved in the occurrence and development of unloading-induced bone loss. 31,32 In the present study, we found that lncRNA OGRU is downregulated during unloading and upregulated during osteoblast differentiation. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading and attenuated the suppression of MC3T3-E1 cell differentiation by unloading conditions in vitro.…”

Section: Introductionsupporting

confidence: 60%

“…46 In particular, the lncRNA H19 (H19) is a key regulator of osteoblast function and is involved in the development of disuse osteoporosis, suggesting that lncRNAs may play a key role in unloading-induced bone loss. 31,32,47,48 Our previous work found many lncRNAs that are significantly differentially expressed in MC3T3-E1 cells under clinorotation unloading condition for 48 h. Further exploration identified a novel unloading-sensitive lncRNA, OGRU, which promotes the osteoblast activity and matrix mineralization and attenuates the osteogenic impairment of MC3T3-E1 cells induced by clinorotation unloading. To further determine whether OGRU can rescue unloading-induced bone loss in vivo, pcDNA3.1(+)-OGRU was delivered via (DSS) 6 -liposomes to bone formation surfaces in HLU mice.…”

Section: Discussionmentioning

confidence: 92%

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Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

Wang

et al. 2019

Preprint

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Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)-OGRU via (DSS) 6 -liposome delivery to the bone formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU can function as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of the OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.

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Section: Introductionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 92%

Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

Wang

et al. 2019

Preprint

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“…Several reports have announced the interaction between lncRNAs and osteogenic transcriptional factors. Li et al indicated that lncRNA H19 was positively correlated with RUNX2 (B. Li et al, , ). While the influence of lncRNAs on TCF7/LEF1 was rarely reported.…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Wang

et al. 2019

Journal Cellular Physiology

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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.

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“…The researchers subsequently showed a strong osteogenic effect of H19 via negatively regulating the NOTCH1 pathway. In 2018, Liu et al confirmed that DNMT1 expression was significantly enhanced in disuse osteoporosis and resulted in 5-methylcytosine cumulation in the H19 promoter, which accompanied by low expression of lncRNA H19 and suppression of the ERK signaling [39]. This evidence revealed the crucial function of H19 methylation in controlling skeletal metabolism.…”

Section: Lncrnasmentioning

confidence: 99%

“…Li et al [39] lncRNA ANRIL DNA methylation of CDKN2A promoter mediated ANRIL expression and altered the binding of the transcription factor, which was inversely associated with bone size, bone density, and mineralization.…”

Section: Osteogenic Differentiationmentioning

confidence: 99%

DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases

Xia

Cen

et al. 2020

Stem Cell Res Ther

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Bone diseases such as osteoarthritis, osteoporosis, and bone tumor present a severe public health problem. Osteogenic differentiation is a complex process associated with the differentiation of different cells, which could regulate transcription factors, cytokines, many signaling pathways, noncoding RNAs (ncRNAs), and epigenetic modulation. DNA methylation is a kind of stable epigenetic alterations in CpG islands without DNA sequence changes and is involved in cancer and other diseases, including bone development and homeostasis. ncRNAs can perform their crucial biological functions at the RNA level, and many findings have demonstrated essential functions of ncRNAs in osteogenic differentiation. In this review, we highlight current researches in DNA methylation of two relevant ncRNAs, including microRNAs and long noncoding RNAs, in the initiation and progression of osteogenesis and bone diseases.

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Overexpression of DNMT1 leads to hypermethylation of H19 promoter and inhibition of Erk signaling pathway in disuse osteoporosis

Cited by 53 publications

References 30 publications

Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

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

DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases

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