MicroRNA-322 (miR-322) and Its Target Protein Tob2 Modulate Osterix (Osx) mRNA Stability

Gámez, Beatriz; Rodríguez-Carballo, Eddie; Bartrons, Ramón; Rosa, José Luís; Ventura, Francesc

doi:10.1074/jbc.m112.432104

Cited by 74 publications

(60 citation statements)

References 55 publications

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“…For instance, Li et al (2008) conducted a miRNA screening during BMP2-induced osteogenesis in C2C12 cells and found that the expression of almost all miRNAs was downregulated during osteoblast differentiation. These data have been confirmed by other groups (Gamez et al 2013). The same authors also described miR-133 and miR-135 as negative regulators of osteogenesis that act by directly targeting Runx2 and Smad5 respectively, thereby inhibiting osteogenic differentiation (Li et al 2008).…”

Section: The Interplay Between Mirnas and Bmp Signalingsupporting

confidence: 75%

“…downregulated, thus avoiding Dlx5 and Osx miRNArelated repression (Itoh et al 2009). The expression of miR-322 is also downregulated by BMP2 and has been shown to indirectly repress Osx expression to facilitate further osteogenic differentiation (Gamez et al 2013).…”

Section: The Interplay Between Mirnas and Bmp Signalingmentioning

confidence: 99%

“…The 3 0 -UTR of the ACVR1/ALK2 gene has recently been studied in vitro to elucidate miRNAs that when expressed induce BMP signaling alterations in fibrodysplasia ossificans progressiva (Mura et al 2012). Several additional BMP-modulated miRNAs have been identified (Li et al 2008, 2009a, Lin et al 2009, Bae et al 2012, Gamez et al 2013, generally as a result of high-throughput expression analysis but without precise information on their transcriptional control and function.…”

Section: The Interplay Between Mirnas and Bmp Signalingmentioning

confidence: 99%

“…Fine-tuning of Osx expression by miRNAs is also observed in the miR-322/Tob2 feedback mechanism in vitro. The Tob2 protein specifically controls the decay of Osx mRNA by regulation of its mRNA deadenylation, while BMP2 represses miR-322 expression and reduces miR-322 binding to the Tob2 3 0 -UTR; thus, higher Tob2 protein levels would control Osx levels (Gamez et al 2013). Changes in miR-637 levels have the capacity to maintain the balance between osteoblast and adipocyte differentiation in hMSCs by the inhibition of OSX expression and activation of adipogenic markers such as peroxisome proliferator-activated receptor g (PPARg (PPARG)) and CCAAT/enhancer-binding protein a (c/EBPa (CEBPA)) (Zhang et al 2011c).…”

Section: Mirnas and Osteoblast Differentiationmentioning

confidence: 99%

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MicroRNAs and post-transcriptional regulation of skeletal development

Gámez¹,

Rodríguez-Carballo²,

Ventura³

2014

Journal of Molecular Endocrinology

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MicroRNAs (miRNAs) have become integral nodes of post-transcriptional control of genes that confer cellular identity and regulate differentiation. Cell-specific signaling and transcriptional regulation in skeletal biology are extremely dynamic processes that are highly reliant on dose-dependent responses. As such, skeletal cell-determining genes are ideal targets for quantitative regulation by miRNAs. So far, large amounts of evidence have revealed a characteristic temporal miRNA signature in skeletal cell differentiation and confirmed the essential roles that numerous miRNAs play in bone development and homeostasis. In addition, microarray expression data have provided evidence for their role in several skeletal pathologies. Mouse models in which their expression is altered have provided evidence of causal links between miRNAs and bone abnormalities. Thus, a detailed understanding of the function of miRNAs and their tight relationship with bone diseases would constitute a powerful tool for early diagnosis and future therapeutic approaches.

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Section: The Interplay Between Mirnas and Bmp Signalingsupporting

confidence: 75%

Section: The Interplay Between Mirnas and Bmp Signalingmentioning

confidence: 99%

Section: The Interplay Between Mirnas and Bmp Signalingmentioning

confidence: 99%

Section: Mirnas and Osteoblast Differentiationmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNAs and post-transcriptional regulation of skeletal development

Gámez¹,

Rodríguez-Carballo²,

Ventura³

2014

Journal of Molecular Endocrinology

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“…miRNA microarray profiling was carried out using the Agilent platform (Genotypic Technology Private Ltd.). Quantitative PCRs were performed using the StepOne real-time PCR system and a TaqMan 5Ј nuclease probe method (Applied Biosystems) (miRNA transcripts normalized to U6) (13)(14)(15).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA 874-3p Exerts Skeletal Anabolic Effects Epigenetically during Weaning by Suppressing Hdac1 Expression

Kushwaha

Khedgikar

Sharma

et al. 2016

Journal of Biological Chemistry

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Embryonic skeletogenesis and postnatal bone development require the transfer of calcium from the mother to the offspring during pregnancy and lactation. Therefore, bone resorption in the mother becomes elevated during these periods, resulting in significant maternal skeletal loss. There follows an anabolic phase around weaning during which there is a remarkable recovery of the maternal skeleton. However, the mechanism(s) of this anabolic response remain(s) largely unknown. We identified eight differentially expressed miRNAs by array profiling, of which miR-874-3p was highly expressed at weaning, a time when bone loss was noted to recover. We report that this weaning-associated miRNA is an anabolic target. Therefore, an agomir of miR-874-3p induced osteoblast differentiation and mineralization. These actions were mediated through the inhibition of Hdac1 expression and enhanced Runx2 transcriptional activation. When injected in vivo, the agomir significantly increased osteoblastogenesis and mineralization, reversed bone loss caused by ovariectomy, and increased bone strength. We speculate that elevated miR-874-3p expression during weaning enhances bone formation and that this miRNA may become a therapeutic target for conditions of bone loss.

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Characterization and assessment of potential microRNAs involved in phosphate‐induced aortic calcification

Fakhry

Skafi

Fayyad‐Kazan

et al. 2017

Journal Cellular Physiology

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Medial artery calcification, a hallmark of type 2 diabetes mellitus and chronic kidney disease (CKD), is known as an independent risk factor for cardiovascular mortality and morbidity. Hyperphosphatemia associated with CKD is a strong stimulator of vascular calcification but the molecular mechanisms regulating this process remain not fully understood. We showed that calcification was induced after exposing Sprague-Dawley rat aortic explants to high inorganic phosphate level (P , 6 mM) as examined by Alizarin red and Von Kossa staining. This calcification was associated with high Tissue-Nonspecific Alkaline Phosphatase (TNAP) activity, vascular smooth muscle cells de-differentiation, manifested by downregulation of smooth muscle 22 alpha (SM22α) protein expression which was assessed by immunoblot analysis, immunofluorescence, and trans-differentiation into osteo-chondrocyte-like cells revealed by upregulation of Runt related transcription factor 2 (Runx2), TNAP, osteocalcin, and osteopontin mRNA levels which were determined by quantitative real-time PCR. To unravel the possible mechanism(s) involved in this process, microRNA (miR) expression profile, which was assessed using TLDA technique and thereafter confirmed by individual qRT-PCR, revealed differential expression 10 miRs, five at day 3 and 5 at day 6 post P treatment versus control untreated aortas. At day 3, miR-200c, -155, 322 were upregulated and miR-708 and 331 were downregulated. After 6 days of treatment, miR-328, -546, -301a were upregulated while miR-409 and miR-542 were downregulated. Our results indicate that high P levels trigger aortic calcification and modulation of certain miRs. These observations suggest that mechanisms regulating aortic calcification might involve miRs, which warrant further investigations in future studies.

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MicroRNA-322 (miR-322) and Its Target Protein Tob2 Modulate Osterix (Osx) mRNA Stability

Cited by 74 publications

References 55 publications

MicroRNAs and post-transcriptional regulation of skeletal development

MicroRNAs and post-transcriptional regulation of skeletal development

MicroRNA 874-3p Exerts Skeletal Anabolic Effects Epigenetically during Weaning by Suppressing Hdac1 Expression

Characterization and assessment of potential microRNAs involved in phosphate‐induced aortic calcification

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