Down-regulation of miRNA-221 triggers osteogenic differentiation in human stem cells

Bakhshandeh, Behnaz; Hafizi, Maryam; Ghaemi, Nasser; Soleimani, Masoud

doi:10.1007/s10529-012-0934-3

Cited by 41 publications

(27 citation statements)

References 33 publications

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“…It was discovered that significantly different levels of miR-221 were present in NAF and DAF. This finding is consistent with the previous study in human unrestricted somatic stem cells and mesenchymal stem cells 16 . In addition, we confirmed that overexpression of miR-221 with lentivirus suppressed the osteogenic potential and that miR-221 played its role via the BMP2-Smad pathways.…”

Section: Discussionsupporting

confidence: 94%

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miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells

et al. 2016

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Background In the moderate and end stages of intervertebral disc (IVD) degeneration, endochondral ossifications are found in the IVD. Purpose To investigate whether endochondral ossification in the late stages of disc degeneration is due to the differentiation of resident progenitor cell in the annulus fibrosus (AF) and the potential signaling pathways in vitro. Study Design An in vitro study of AF cell osteogenic differentiation and possible mechanisms Methods Normal AF (NAF) and degenerated AF (DAF) cells were isolated from tissue removed surgically from juvenile patients with idiopathic scoliosis and adult patients with degenerative scoliosis. Osteogenic differentiation was investigated using quantitative RT-PCR and histology. Effects of miR-221 on osteogenesis were measured by overexpression of miR-221 with lentivirus. BMP2 and phospho-Smad protein were detected by Western blotting. Results Both NAF and DAF cells underwent osteogenic differentiation, which, was confirmed by detecting mineralization of the cell cultures and by an increase in the expression mRNAs for BMP2, Runx2, ALP, and Osteocalcin. DAF cells exhibited increased osteogenic differentiation potential over the NAF cells. By contrast to the elevated phospho-Smads, the basal level of miR-221 significantly decreased in DAF cells compared with NAF cells. Cultures of both cell types in osteogenic medium showed a decrease in miR-221 expression while overexpression of miR-221 markedly decreased the level of BMP2, phospho-Smads and the expression of osteogenic genes in DAF cells. The osteogenic potential of DAF cells diminished by the overexpression of miR-221. Conclusion Compared to NAF cells, AF cells from degenerated discs have a greater tendency for osteogenic differentiation, which involves the BMP-Smad pathways and can be regulated by miR-221. These observations may be developed into a therapeutic to prevent the endochondral ossification.

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Section: Discussionsupporting

confidence: 94%

“…miR-221 and miR-222 promote cell cycle progression and proliferation by targeting cyclin-dependent kinase inhibitors p27 and p57 15 . Knockdown of miR-221 in human unrestricted somatic stem cells and mesenchymal stem cells increased the expression of the osteogenic genes osteopontin and osteocalcin 16 .…”

Section: Introductionmentioning

confidence: 99%

miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells

et al. 2016

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“…miR-21 can induce differentiation of colon stem cells,39 miR-143 and miR-145 can inhibit the stem cell characteristics of PC3 cells,40 miR-223 is expressed in leukemic stem cells41 and miR-320 suppresses stem cell characteristics of prostate cells through regulation of Wnt signalling 42. In line with our data, it was noted that regulators of MSCs/osteoblast differentiation were prominent: miR-99, miR-125b, miR-152, miR-320 and miR-345 play roles in MSCs43–45 and miR-221 functions in osteoblast differentiation 46. This may be linked to the propensity of PCa to metastasise to bone.…”

Section: Resultssupporting

confidence: 86%

Enhanced regulation of cell cycle and suppression of osteoblast differentiation molecular signatures by prostate cancer stem-like holoclones

et al. 2015

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“…Meanwhile, we have summarized that H 2 S regulated the miRNAs in Part 6.2, such as miR-221, miR-1, miR-133a, miRNA-135a-5p and miRNA-485-5p, but all these results were obtained from other disease research, whether these miRNAs related to bone disease? Some reports also found that downregulation of miR-221 can trigger osteogenic differentiation of in human stem cells [74], downregulation of miR-1 during BMP-2-induced osteogenesis [75], miR-133a was upregulated in osteoblast-like periodontal ligament stem cells and inhibit osteoclastogenesis in circulating monocytes [76], miRNA-135a-5p and miRNA-485-5p also involved in the process of bone remodeling. However, whether H 2 S regulate above miRNAs and then maintain the bone health still need more evidence.…”

Section: Discussion and Future Research Directionsmentioning

confidence: 99%

Cross-talk of MicroRNA and hydrogen sulfide: A novel therapeutic approach for bone diseases

Zhai

Tyagi

2017

Biomedicine & Pharmacotherapy

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Bone homeostasis requires a balance between the bone formation of osteoblasts and bone resorption of osteoclasts to maintain ideal bone mass and bone quality. An imbalance in bone remodeling processes results in bone metabolic disorders such as osteoporosis. Hydrogen sulfide (H2S), a gasotransmitter, has attracted the focus of many researchers due to its multiple physiological functions. It has been implicated in anti-inflammatory, vasodilatory, angiogenic, cytoprotective, anti-oxidative and anti-apoptotic mechanisms. H2S has also been shown to exert osteoprotective activity through its anti-inflammatory and anti-oxidative effects. However, the underlying molecular mechanisms by which H2S mitigates bone diseases are not completely understood. Experimental evidence suggests that H2S may regulate signaling pathways by directly influencing a gene in the cascade or interacting with some other gasotransmitter (carbon monoxide or nitric oxide) or both. MicroRNAs (miRNAs) are short non-coding RNAs which regulate gene expression by targeting, binding and suppressing mRNAs; thus controlling cell fate. Certainly, bone remodeling is also regulated by miRNAs expression and has been reported in many studies. MicroRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new possibility for exploring the H2S-microRNA crosstalk in bone diseases. However, the relationship between miRNAs, bone development, and H2S is still not well explained. This review focuses on miRNAs and their roles in regulating bone remodeling and possible mechanisms behind H2S mediated bone loss inhibition, H2S-miRNAs crosstalk in relation to the pathophysiology of bone remodeling, and future perspectives for miRNA-H2S as a therapeutic agent for bone diseases.

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Down-regulation of miRNA-221 triggers osteogenic differentiation in human stem cells

Cited by 41 publications

References 33 publications

miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells

miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells

Enhanced regulation of cell cycle and suppression of osteoblast differentiation molecular signatures by prostate cancer stem-like holoclones

Cross-talk of MicroRNA and hydrogen sulfide: A novel therapeutic approach for bone diseases

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