MiRNAs in Bone Diseases

Background/Aims: Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs. Methods: First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214. Results: MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214. Conclusions: MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis.L. Yang and D. Ge contributed to the work equally.

show abstract

“…Previous studies have demonstrated that miRNAs played an important role in the development of osteoporosis [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

Yang

Ge²,

Cao³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Recent studies have suggested the regulatory functions of miRNAs in periodontitis involved in bone remodeling (Yan et al, 2017). Recent experimental reports have demonstrated that miRNAs participate in every step of bone formation and bone homeostasis from embryonic bone development to adult bone tissue maintenance by regulating the differentiation, growth, and activity of different cell systems inside and outside the skeleton (Moore & Xiao, 2013). The miRNAs have been shown to regulate cell proliferation and may be related to directed differentiation (Chen et al, 2014;Huang, Geng, Wei, Zhang, & Jiang, 2016).…”

Section: Discussionmentioning

confidence: 99%

The miR‐3940‐5p inhibits cell proliferation of gingival mesenchymal stem cells

et al. 2019

View full text Add to dashboard Cite

Objectives Drug‐induced gingival overgrowth (DIGO) is a well‐recognized side effect of nifedipine (NIF). However, the molecular mechanisms of DIGO are still unknown. Here, we explored the possible role of miR‐3940‐5p in DIGO using NIF‐treated gingival mesenchymal stem cells (GMSCs). Material and methods CFSE and cell cycle assays were used to examine cell proliferation. The alkaline phosphatase (ALP) activity assay, Alizarin Red staining, quantitative calcium analysis, and osteogenesis‐related gene expression were used to examine osteo/dentinogenic differentiation. Results The CFSE assay showed that NIF enhanced cell proliferation, and the over‐expression of miR‐3940‐5p inhibited the proliferation of GMSCs with or without NIF stimulation. Cell cycle assays revealed that the cell cycle was arrested at the G0/G1 phase. Furthermore, it was found that the over‐expression of miR‐3940‐5p upregulated p15INK4b, p18INK4c, p19INK4d, and Cyclin A and downregulated Cyclin E in GMSCs with or without NIF treatment. In addition, the over‐expression of miR‐3940‐5p enhanced ALP activity and mineralization in vitro and increased the expression of the osteo/dentinogenic differentiation markers DSPP and DMP1 and the key transcription factor DLX5 in GMSCs. Conclusions miR‐3940‐5p inhibited cell proliferation, enhanced the osteo/dentinogenic differentiation of GMSCs, and might play a role in DIGO as a potent agent in the treatment of nifedipine‐induced gingival overgrowth.

show abstract

“…Numerous studies have demonstrated that alterations in miRNA expression are strongly linked to various kinds of human diseases, including cancers (Adams et al , ), cardiovascular diseases (Latronico and Condorelli, ), inflammatory and autoimmune diseases (Zeng et al , ), and musculoskeletal disorders (Lian et al , ; Moore and Xiao, ). It has been reported that miRNAs have stable property and tissue‐specificity, and might therefore be used as biomarkers for blood‐based diagnosis of diseases (Chen et al , ; Mitchell et al , ).…”

Section: Perspectivesmentioning

confidence: 99%

“…MicroRNAs (MiRNAs) are a type of small non‐coding RNA molecule of 20–22 nucleotides in length, which play important roles in a number of physiological processes, such as individual development (Ying et al , ), organ formation (Joglekar et al , ; Khoshgoo et al , ), tumorigenesis (Lawrie, ; Papaconstantinou et al , ; Zhan et al , ), and cell proliferation, differentiation and apoptosis (Luo et al , ; Mathieu and Ruohola‐Baker, ). Due to the prominent and extensive functions of the miRNA, the miRNA dysexpression or the combinational alteration between miRNA and its target genes will contribute to certain diseases, such as cancer (Tilghman et al , ), autoimmune diseases (Buckland, ) and bone‐related diseases (Moore and Xiao, ). Interestingly, some miRNAs, such as miR‐155 (Wang et al , ), miR‐146a (Zhao et al , ) and miR‐377 (Tsirimonaki et al , ), are present in intervertebral disc (IVD), and their dysregulation in IDD might serve as potential biomarkers for the early diagnosis of IDD.…”

Section: Introductionmentioning

confidence: 99%

The roles and perspectives of microRNAs as biomarkers for intervertebral disc degeneration

Zhou

Chen

Grad

et al. 2017

J Tissue Eng Regen Med

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are highly conserved molecules that regulate protein levels post-transcriptionally. Aberrant miRNA expression presents in various musculoskeletal disorders, such as osteoporosis, osteoarthritis and rheumatoid arthritis. The expression levels of miRNAs are characterized by endogenous properties and tissue specificity. This raises the possibility that miRNAs could serve as useful clinical biomarkers in the diagnosis of certain diseases. Intervertebral disc degeneration (IDD) is one of the major causes of back pain, and a process characterized by a cascade of molecular, cellular, biochemical and structural changes. The presence of dysregulated miRNA expression in patients with disc degeneration diseases indicates that miRNAs may play a vital role in the pathogenesis of IDD. Here, we provide an introduction of the roles of miRNAs in the process of IDD, and the prospective application of miRNAs as biomarkers for IDD. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

MiRNAs in Bone Diseases

Cited by 28 publications

References 0 publications

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1

The miR‐3940‐5p inhibits cell proliferation of gingival mesenchymal stem cells

The roles and perspectives of microRNAs as biomarkers for intervertebral disc degeneration

Contact Info

Product

Resources

About