miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2

Yu, Shuang; Zheng, Lihua; Zeng, Bin; Inose, Hiroyuki; Wang, Ji; Grosschedl, Rudolf; Karsenty, Gérard

doi:10.1084/jem2096oia10

Cited by 27 publications

(38 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these, miR-34c, miR-30a, miR-29b, and miR-188 have been reported to negatively or positively miR-503 inhibits stretch-induced osteogenesis L. Liu et al regulate osteogenesis (Zhang et al, 2011b;Wu et al, 2012;Trompeter et al, 2013;Li et al, 2015a, b). MiR-34s (miR-34b, -34c) inhibit osteoblast proliferation by suppressing Cyclin D1, CDk4, and CDK6 accumulation while simultaneously attenuating terminal osteoblast differentiation partly through the inhibition of SATB2 (Wei et al, 2012). MiR-30 family members (miR-30a, -30b, -30c, and -30d) may function as crucial negative regulators during BMP-2mediated osteogenic differentiation by targeting Smad1 and Runx2 (Eguchi et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐503‐5p inhibits stretch‐induced osteogenic differentiation and bone formation

Liu

et al. 2016

Cell Biology International

View full text Add to dashboard Cite

Cyclical stretch-induced bone formation during orthodontic treatment is a complex biological process modulated by various factors including miRNAs and their targeted-gene network. However, the miRNA expression profile and their roles in osteogenic differentiation of bone mesenchymal stem cells (BMSCs) exposed to mechanical stretch remains unclear. Here, we use the miRNA microarray assay to screen for mechano-sensitive miRNAs during stretch-induced osteogenic differentiation of BMSCs and identified that nine miRNAs were differentially expressed between stretched and control BMSCs. Furthermore, miR-503-5p, which was markedly downregulated in both microarray assay and qRT-PCR assay were selected for further functional verification. We found that overexpression of miR-503-5p in BMSCs attenuated stretch-induced osteogenic differentiation while the effect was reversed by miR-503-5p inhibition treatment. In vivo studies, overexpression of miR-503-5p with specific agomir decreased Runx2, ALP mRNA, and protein expression, decreased osteoblast numbers and osteoblastic bone formation in the OTM tension sides. In conclusion, our study revealed that miR-503-5p functions as the mechano-sensitive miRNA and inhibits BMSCs osteogenic differentiation subjected to mechanical stretch and bone formation in OTM tension sides.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA‐503‐5p inhibits stretch‐induced osteogenic differentiation and bone formation

Liu

et al. 2016

Cell Biology International

View full text Add to dashboard Cite

show abstract

“…Recently, numerous studies have revealed that miRNAs play critical roles in osteoblast differentiation. For example, miR-34s was reported to inhibit osteoblast differentiation by targeting Special AT-rich sequence-binding protein 2 (SATB2) [10]. MiR-100 suppressed osteoblast differentiation by inhibiting bone morphogenetic protein receptor type II (BMPR2) [11].…”

Section: Introductionmentioning

confidence: 99%

miR‐145 suppresses osteogenic differentiation by targeting Sp7

et al. 2013

View full text Add to dashboard Cite

a b s t r a c tOsteogenesis depends on a coordinated network of transcription factors including Sp7. Emerging evidence indicates that microRNAs (miRNAs) act as pivotal regulators in various biological processes including osteoblast proliferation and differentiation. Here, we investigated the effect of miR-145 on osteogenic differentiation. miR-145 was decreased during osteogenic differentiation, which could suppress the osteogenic differentiation of C 2 C 12 and MC3T3-E1 cells confirmed by gain-and loss-of-function experiments. Moreover, bioinformatic analysis combined with luciferase reporter assay, and Western blot validated that miR-145 negatively regulated Sp7 expression. Inhibition of Sp7 showed similar effect with miR-145 on osteogenic differentiation, whereas overexpression of Sp7 attenuated this effect. Collectively, these data indicate that miR-145 is a novel regulator of Sp7, and it suppresses the osteogenic differentiation of C 2 C 12 and MC3T3-E1 cells.

show abstract

“…2,3,24,25 SATB2 is required for early OB differentiation and its expression is turned off during terminal stages of differentiation by miR-34b/c and 23a~27a~24-2 clusters. 25,26 Here, we demonstrate that the expression of SATB2 is higher in OS cells and tumors compared with normal OBs, the putative cell of origin for OS. This suggests that OB progenitors expressing high levels of SATB2 either may have failed to undergo normal differentiation or may have undergone additional genetic events leading to malignant transformation, both of which may partially be due to high SATB2 expression.…”

Section: Discussionmentioning

confidence: 60%

“…The use of SATB2 as an immunohistochemical maker for OS has also recently been reported by Conner which SATB2 is upregulated in OS has not been determined, both miR-31 and 34b/c have been shown to target SATB2 transcripts and these miRNA clusters have been implicated in metastases and bone differentiation. 8,25 Thus, further studies to elucidate SATB2 upstream regulation may provide insights into miRNA pathways involved in the progression of OS.…”

Section: Discussionmentioning

confidence: 99%

SATB2 enhances migration and invasion in osteosarcoma by regulating genes involved in cytoskeletal organization

et al. 2014

View full text Add to dashboard Cite

Osteosarcoma (OS) is the most common malignant bone tumor and the majority of recurrences are due to metastasis. However, the molecular mechanisms that regulate OS metastatic spread are largely unknown. In this study, we report that special AT-rich-binding protein 2 (SATB2) is highly expressed in OS cells and tumors. Short hairpin RNA-mediated knockdown of SATB2 (sh-SATB2) decreases migration and invasion of OS cells without affecting proliferation or viability. Microarray analysis identified genes that were differentially regulated by SATB2 including the actin-binding protein Epithelial Protein Lost In Neoplasm (EPLIN), which was upregulated in sh-SATB2 cells. Silencing EPLIN rescues the decreased invasion observed in sh-SATB2 cells. Pathway analyses of SATB2-regulated genes revealed enrichment of those involved in cytoskeleton dynamics, and increased stress fiber formation was detected in cells with SATB2 knockdown. Furthermore, sh-SATB2 cells exhibit increased RhoA, decreased Rac1 and increased phosphorylation of focal adhesion kinase (FAK) and paxillin. These findings identify SATB2 as a novel regulator of OS invasion, in part via effects on EPLIN and the cytoskeleton.

show abstract

miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2

Cited by 27 publications

References 39 publications

MicroRNA‐503‐5p inhibits stretch‐induced osteogenic differentiation and bone formation

MicroRNA‐503‐5p inhibits stretch‐induced osteogenic differentiation and bone formation

miR‐145 suppresses osteogenic differentiation by targeting Sp7

SATB2 enhances migration and invasion in osteosarcoma by regulating genes involved in cytoskeletal organization

Contact Info

Product

Resources

About