MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast differentiation by regulating β-catenin acetylation

Ko, Jih‐Yang; Chuang, Pei-Chin; Chen, Mingwen; Ke, Huei-Ching; Wu, Shin-Long; Chang, Yu‐Hsuan; Chen, Yu‐Shan; Wang, Feng‐Sheng

doi:10.1016/j.bone.2013.09.019

Cited by 59 publications

(53 citation statements)

References 40 publications

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“…So far only miR-29a has been reported to ameliorate glucocorticoid-induced suppression of osteoblast differentiation by regulating Wnt/β-catenin pathway. 33,34 In this study, we found that overexpression of miR-216a can significantly rescue the suppressive effects of DEX on the osteoblast differentiation of hAMSCs, which suggested that therapeutic upregulation of miR-216a in MSCs may promote bone formation and even reverse osteoporosis. With the development of miRNA delivery system, which can Damage of the bone formation potential of MSCs is responsible for the bone loss incurred in aging and osteoporosis.…”

Section: Discussionmentioning

confidence: 63%

“…[30][31][32] However, to date, only a few miRNAs have been reported to be antagonists for the suppression of glucocorticoids during osteogenic differentiation. 33,34 In this study, we revealed that miR-216a promotes the osteogenic differentiation of human adipose-derived MSCs (hAMSCs) in vitro and enhances bone formation in vivo. Moreover, we demonstrated that a high concentration of dexamethasone (DEX) inhibits osteogenic differentiation, whereas miR-216a antagonizes the suppressive effect of DEX on osteogenic differentiation.…”

mentioning

confidence: 98%

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miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway

Li¹,

Li²,

Fan³

et al. 2015

Cell Death Differ

117

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Osteoporosis is a disease marked by reduced bone mass, leading to an increased risk of fractures or broken bones. Bone formation is mediated by recruiting mesenchymal stem cells (MSCs). Elucidation of the molecular mechanisms that regulate MSC differentiation into osteoblasts is of great importance for the development of anabolic therapies for osteoporosis and other bone metabolism-related diseases. microRNAs (miRNAs) have been reported to have crucial roles in bone development, osteogenic differentiation and osteoporosis pathophysiology. However, to date, only a few miRNAs have been reported to enhance osteogenesis and regulate the suppressive effect of glucocorticoids on osteogenic differentiation. In this study, we discovered that miR-216a, a pancreatic-specific miRNA, was significantly upregulated during osteogenic differentiation in human adiposederived MSCs (hAMSCs). The expression of miR-216a was positively correlated with the expression of bone formation marker genes in clinical osteoporosis samples. Functional analysis demonstrated that miR-216a can markedly promote osteogenic differentiation of hAMSCs, rescue the suppressive effect of dexamethasone (DEX) on osteogenic differentiation in vitro and enhance bone formation in vivo. c-Cbl, a gene that encodes a RING finger E3 ubiquitin ligase, was identified as a direct target of miR-216a. Downregulation of c-Cbl by short hairpin RNAs can mimic the promotion effects of miR-216a and significantly rescue the suppressive effects of DEX on osteogenesis. Pathway analysis indicated that miR-216a regulation of osteogenic differentiation occurs via the c-Cbl-mediated phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The recovery effects of miR-216a on the inhibition of osteogenesis by DEX were attenuated after blocking the PI3K pathway. Thus, our findings suggest that miR-216a may serve as a novel therapeutic agent for the prevention and treatment of osteoporosis and other bone metabolism-related diseases.

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Section: Discussionmentioning

confidence: 63%

mentioning

confidence: 98%

miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway

Li¹,

Li²,

Fan³

et al. 2015

Cell Death Differ

117

View full text Add to dashboard Cite

show abstract

“…Negative calcium balance can compensatorily increase blood phosphorus level by promoting the release of phosphorus in bone matrix into blood and can further promote the release of calcium in bone matrix into blood [21]. These glucocorticoids-induced changes can increase bone resorption, which compensatorily increase ALP activity to promote bone formation [22]. The glucocorticoids-induced bone resorption and abnormal bone reconstruction lead to the occurrence of OP.…”

Section: Discussionmentioning

confidence: 99%

Pinoresinol diglucoside exhibits protective effect on dexamethasone-induced osteoporosis in rats

Zhang¹,

Min²,

Wang³

et al. 2016

Trop. J. Pharm Res

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“…Clinical investigations and mouse model experiments have confirmed that chronic GC treatment elevates Wnt inhibitor levels (Dickkopf-1 [DKK1] and secreted Frizzled-related protein [sFRP]) in sera as well as bone marrow [60-63]. Besides, GC also blocks this pathway through, first, downregulating β-catenin level [64] and, second, impairing TCF transcriptional activities through recruiting HDAC1 to their target promoters [65]. As discussed before, inhibition of the Wnt pathway leads to impaired osteogenesis, but promotes adipocytic differentiation.…”

Section: Changed Bone Marrow Microenvironment Under Pathological Condmentioning

confidence: 99%

“…Our previous research proved that during osteoblastogenesis, the inhibited Wnt/β-catenin pathway by dexamethasone treatment promotes C/EBPα expression due to downregulated DNA methylation at its promoter [22]. In addition, changed microRNA expression profiles might also help to mediate the inhibitory effect of GC on osteoblastic differentiation [64, 66]. Thereby, a conclusion could be drawn through these in vivo and in vitro studies that excessive GC in bone marrow helps to establish both active and repressive epigenetic signatures on adipogenic and osteogenic promoters, respectively, by networking with lineage-related cell signals and transcriptional factors.…”

Section: Changed Bone Marrow Microenvironment Under Pathological Condmentioning

confidence: 99%

Osteoblast versus Adipocyte: Bone Marrow Microenvironment-Guided Epigenetic Control

Zuo

Zhang

et al. 2018

Case Rep Orthop Res

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The commitment and differentiation of bone marrow mesenchymal stem cells (MSCs) is tightly controlled by the local environment ensuring lineage differentiation balance and bone homeostasis. However, pathological conditions linked with osteoporosis have changed the bone marrow microenvironment, shifting MSCs’ fate to favor adipocytes over osteoblasts, and consequently leading to decreased bone mass with marrow fat accumulation. Multiple questions related to the underlying mechanisms remain to be answered. As recent findings have confirmed the fundamental role of the epigenetic mechanism in connecting environmental signals with gene expression and stem cell differentiation, a regulatory network in the bone marrow microenvironment, epigenetic modulation, gene expression, and MSC differentiation begins to emerge. This review discusses how pathological environmental factors affect MSCs’ fate by epigenetic modulating lineage-specific genes. We conclude that manipulating local environments and/or the epigenetic regulatory machinery that target the adipocyte differentiation pathway might be a therapeutic implication of bone loss diseases such as osteoporosis.

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MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast differentiation by regulating β-catenin acetylation

Cited by 59 publications

References 40 publications

miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway

miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway

Pinoresinol diglucoside exhibits protective effect on dexamethasone-induced osteoporosis in rats

Osteoblast versus Adipocyte: Bone Marrow Microenvironment-Guided Epigenetic Control

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