Estrogen inhibits osteoclasts formation and bone resorption via microRNA‐27a targeting PPARγ and APC

Guo, Lei; Chen, Kaizhe; Yuan, Jun; Huang, Ping; Xu, Xing; Li, Changwei; Qian, Nan; Qi, Jin; Shao, Zhiliang; Deng, Lianfu; He, Chuan; Xu, Jian

doi:10.1002/jcp.26788

Cited by 49 publications

(40 citation statements)

References 40 publications

(62 reference statements)

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“…In postmenopausal osteoporosis, estrogen therapy effectively prevents bone loss ( 39 ). Emerging evidence has demonstrated that estrogen exhibits an inhibitory role in osteoclast formation and enhances osteoblast function ( 40 , 41 ). During estrogen-decreased osteoclast differentiation, miR-27a remarkably enhances the inhibitory effect of estrogen ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence has demonstrated that estrogen exhibits an inhibitory role in osteoclast formation and enhances osteoblast function ( 40 , 41 ). During estrogen-decreased osteoclast differentiation, miR-27a remarkably enhances the inhibitory effect of estrogen ( 40 ). In addition, following treatment with antiosteoporotic agents, serum miR-27a levels are significantly reduced in postmenopausal women ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

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miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

Liu

Zhu

et al. 2020

Mol Med Rep

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osteoporosis is a complex multifactorial disorder characterized by microarchitectural deterioration, low bone mass, and increased risk of fractures or broken bones. Balanced bone remodeling is tightly regulated by the differentiation, activity and apoptosis of bone-forming osteoblasts and bone-resorbing osteoclasts. Micrornas (mirs) are dysregulated in osteoporosis, but whether they control osteogenic differentiation and skeletal biology, or could serve as therapeutic targets remains to be elucidated. The present study identified miR-27a-3p as a critical suppressor of osteoblastogenesis. Bioinformatics analysis and luciferase reporter assays demonstrated that miR-27a-3p directly targeted and controlled the expression of osterix (osx), an early response gene essential for bone formation, through its 3'-untranslated region. miR-27a-3p functionally inhibited the differentiation of preosteoblasts by decreasing osx expression, which synergistically contributed to bone formation. miR-27a-3p level was significantly decreased during osteogenic differentiation and increased in the serum of patients with osteoporosis. Together, miR-27a-3p contributed to diminished osteogenic function during osteogenic differentiation and might thus serve as a therapeutic target and diagnostic biomarker for osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

Liu

Zhu

et al. 2020

Mol Med Rep

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“…In fact, T-fimbrin is an inhibitor of sealing zone formation and its deletion increases bone resorption (Neugebauer et al, 2018). Finally, APC is involved in the association between vimentin intermediate filaments and microtubules (Leduc et al, 2015) and as described above, APC appears important in organizing the podosome belt and for bone resorption (Guo et al, 2018;Matsumoto et al, 2013). However, the specific functions of APC and vimentin in osteoclasts are unknown.…”

Section: Intermediate Filaments and Septinsmentioning

confidence: 96%

“…Both EB1 and APC participate in actin-microtubule crosstalk (Dogterom et al, 2019). In osteoclasts, EB1 is required for podosome belt formation (Biosse Duplan et al, 2014) and indirect evidence suggest that APC has an important role at the podosome belt as well as in bone resorption (Guo et al, 2018). Besides AKT, Dock5 also regulates microtubule acetylation and GSK3β activity in osteoclasts (Fig.…”

Section: Actin and Microtubule Crosstalk At The Podosome Beltmentioning

confidence: 97%

The osteoclast cytoskeleton – current understanding and therapeutic perspectives for osteoporosis

Blangy

Bompard

Guérit

et al. 2020

Journal of Cell Science

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Osteoclasts are giant multinucleated myeloid cells specialized for bone resorption, which is essential to preserve bone health throughout life. The activity of osteoclasts relies on the typical organization of osteoclast cytoskeleton components into a highly complex structure comprising actin, microtubules and other cytoskeletal proteins that constitutes the backbone of the bone resorption apparatus. The development of methods to obtain osteoclasts in culture and manipulate them genetically, as well as improvements in cell-imaging technologies, allowed shedding light onto the molecular mechanisms that control the structure and dynamics of the osteoclast cytoskeleton, and thus the mechanism of bone resorption. Although essential for normal bone physiology, abnormal osteoclast activity can cause bone defects, in particular their hyper-activation commonly associated with many pathologies, hormonal imbalance and medical treatments. Increased bone degradation by osteoclasts provokes progressive bone loss, leading to osteoporosis, with the resulting bone frailty resulting in fractures, loss of autonomy and premature death. In this context, the osteoclast cytoskeleton has recently proven to be a relevant therapeutic target for controlling pathological bone resorption levels. Here, we review our present knowledge about the regulatory mechanisms of the osteoclast cytoskeleton that control their bone resorption activity in normal and pathological conditions.

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“…Inhibiting the activity of miR-23a-3p can increase the expression level of LRP5 and thus increase the differentiation of osteoblasts. As a target of miR-27a, APC is inhibited, and miR-27a increases β-catenin to activate the WNT signaling pathway (Guo et al, 2018). Other studies have shown that miR-142-3p regulates APC activation of Wnt/β-catenin Signaling, while Hu et al (2016) have demonstrated that miR-142-3p can directly inhibit the activity of β-catenin in Wnt/β-catenin Signaling.…”

Section: Pathway-level Analysismentioning

confidence: 99%

MicroRNA Alterations for Diagnosis, Prognosis, and Treatment of Osteoporosis: A Comprehensive Review and Computational Functional Survey

Zhang

et al. 2020

Front. Genet.

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Osteoporosis (OP) is a systemic bone disease with a series of clinical symptoms. The use of screening biomarkers in OP management is therefore of clinical significance, especially in the era of precision medicine and intelligent healthcare. MicroRNAs (miRNAs) are small, non-coding RNAs with the potential to regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs may serve as biomarkers for OP prediction and prevention. However, few studies have emphasized the role of miRNAs in systems-level pathogenesis during OP development. In this article, literature-reported OP miRNAs were manually collected and analyzed based on a systems biology paradigm. Functional enrichment studies were performed to decode the underlying mechanisms of miRNAs in OP etiology and therapeutics in three-dimensional space, i.e., integrated miRNA-gene-pathway analysis. In particular, interactions between miRNAs and three well-known OP pathways, i.e., estrogenendocrine, WNT/β-catenin signaling, and RANKL/RANK/OPG, were systematically investigated, and the effects of non-genetic factors on personalized OP prevention and therapy were discussed. This article is a comprehensive review of OP miRNAs, and bridges the gap between an understanding of OP pathogenesis and clinical translation.

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Estrogen inhibits osteoclasts formation and bone resorption via microRNA‐27a targeting PPARγ and APC

Cited by 49 publications

References 40 publications

miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

miR‑27a‑3p negatively regulates osteogenic differentiation of MC3T3‑E1 preosteoblasts by targeting osterix

The osteoclast cytoskeleton – current understanding and therapeutic perspectives for osteoporosis

MicroRNA Alterations for Diagnosis, Prognosis, and Treatment of Osteoporosis: A Comprehensive Review and Computational Functional Survey

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