MiR-26a functions oppositely in osteogenic differentiation of BMSCs and ADSCs depending on distinct activation and roles of Wnt and BMP signaling pathway

Su, Xiaoming; Liao, Li; Yi, Siyan; Jing, Huan; Liu, S; Zhou, Hong; Liu, Y; Jin, Yan

doi:10.1038/cddis.2015.221

Cited by 108 publications

(86 citation statements)

References 55 publications

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“…The osteogenic differentiation of BMSCs in vitro results from the activation of some well‐known molecular signaling pathways, such as mitogen‐activated protein kinase (MAPK) signaling pathway, Wnt/beta‐catenin signaling pathway, TGF‐beta/Smad and BMP signaling pathways. In addition, some osteoblast‐specific signal proteins and osteoblast‐specific transcription factors, including Runx2, Osterix and BMP4, also have been proved to play an important role in the osteogenic differentiation of BMSCs . Besides, substantial evidence shows that the inhibited expressions of adipogenic differentiation transcriptional regulators, such as peroxisome proliferator‐activated receptor γ (PPARγ) and CCAAT/enhancer‐binding protein (C/EBP), could promote the osteogenic differentiation of BMSCs .…”

Section: Introductionmentioning

confidence: 99%

“…In addition, some osteoblast‐specific signal proteins and osteoblast‐specific transcription factors, including Runx2, Osterix and BMP4, also have been proved to play an important role in the osteogenic differentiation of BMSCs . Besides, substantial evidence shows that the inhibited expressions of adipogenic differentiation transcriptional regulators, such as peroxisome proliferator‐activated receptor γ (PPARγ) and CCAAT/enhancer‐binding protein (C/EBP), could promote the osteogenic differentiation of BMSCs . Many studies have already demonstrated that the disruption of the balance between osteogenesis and adipogenesis in BMSCs leads to disorders of skeletal reconstruction .…”

Section: Introductionmentioning

confidence: 99%

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Melatonin protects bone marrow mesenchymal stem cells against iron overload‐induced aberrant differentiation and senescence

Yang

et al. 2017

Journal of Pineal Research

107

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Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem cells which can differentiate into osteoblasts, chondrocytes and adipocytes. Dysfunction of BMSCs in response to pathological stimuli contributes to bone diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be an important mediator in bone formation and mineralization. The aim of this study was to investigate whether melatonin protected against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron overload induced by ferric ammonium citrate (FAC) caused irregularly morphological changes and markedly reduced the viability in BMSCs. Consistently, osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore, exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin as well. Meanwhile, melatonin was able to counter the reduction in cell proliferation by iron overload in BMSCs. In addition, protective effects of melatonin on iron overload-induced dysfunction of BMSCs were abolished by its inhibitor luzindole. Also, melatonin protected BMSCs against iron overload-induced ROS accumulation and membrane potential depolarization. Further study uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein expressions in BMSCs with iron overload. Collectively, melatonin plays a protective role in iron overload-induced osteogenic differentiation dysfunction and senescence through blocking ROS accumulation and p53/ERK/p38 activation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Melatonin protects bone marrow mesenchymal stem cells against iron overload‐induced aberrant differentiation and senescence

Yang

et al. 2017

Journal of Pineal Research

107

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“…MiR-376c inhibits osteoblastogenesis by targeting WNT3 and ARF-GEF-1 -facilitated augmentation of β-catenin transactivation [54]. MiR-26a is majorly target on GSK3β to activate WNT signaling for promoting osteogenic differentiation of BMSCs [55]. In this study, we demonstrated that miR-16-2* can suppress osteoblast differentiation of hBMSCs through regulating WNT5A-mediated WNT pathway.…”

Section: Discussionmentioning

confidence: 70%

miR-16-2* Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells

Duan

Zhao

Xiong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteoporosis is a bone metabolic disease characterized by a systemic impairment of bone mass, which results in increased propensity of fragility fractures. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. Mesenchymal stem cells (MSCs) are induced to differentiate into preosteoblasts, which are regulated by the signaling cascades initiated by the various signals, including miRNAs. miR-16-2* is a newly discovered miRNA that participates in diagnosis and prognosis of hepatocellular carcinoma, cervical cancer and chronic lymphocytic leukemia. However, the effect of miR-16-2* on the regulation of osteoblast differentiation and the mechanism responsible are still unclear. Here we discuss the contribution of miR-16-2* to osteoporosis, osteoblast differentiation and mineralization. Methods: The expression pattern of miR-16-2* during osteogenesis or in osteoporosis bone samples was validated by quantitative real-time PCR (qRT-PCR). The human bone marrow mesenchymal stem cells (hBMSCs) were induced to differentiate into osteoblasts by osteogenic induced medium containing dexamethasone, ascorbate-2-phosphat, beta-glycerophosphate and vitamin-D3. The target genes of miR-16-2* were predicted by TargetScan and PicTar. The mRNA and protein levels of osteogenic key markers were detected using qRT-PCR or western blot respectively. The WNT signal activity was analyzed by TOP/FOP reporter assay. Results: The expression of miR-16-2* in patient bone tissue with osteoporosis was negatively correlated with bone formation related genes. During osteoblast differentiation process, the expression of miR-16-2* was significantly decreased. Upregulation of miR-16-2* in hBMSCs impaired the osteogenic differentiation while the downregulation of miR-16-2* increased this process. Upregulation the expression of miR-16-2* could also block the WNT signal pathway by directly target WNT5A. Furthermore, knockdown of miR-16-2* could promote the activation of RUNX2, possibly by lifting the inhibitory effect of miR-16-2* on WNT pathway. Conclusion: Taken together, we report a novel biological role of miR-16-2* in osteogenesis through regulating WNT5A response for the first time. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.

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“…miR‐26a was widely identified in porcine testicular tissues using RNA‐seq technology (Li, Li, et al., ; Lian et al., ; Luo et al., ; Ran et al., ), suggesting its key roles in swine testicular development and spermatogenesis. Although previous studies reported that miR‐26a plays multiple regulatory roles in cell metabolic processes, including differentiation (Su et al., ), proliferation (Zhou et al., ) and apoptosis (Zhang et al., ). Nevertheless, the regulatory mechanism of miR‐26a is poorly understood in cell autophagy.…”

Section: Discussionmentioning

confidence: 99%

miR‐26a suppresses autophagy in swine Sertoli cells by targeting ULK2

Ran

Cao

et al. 2018

Reprod Domestic Animals

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A large number of microRNAs (miRNAs) have been detected from porcine testicular tissues thanks to the development of high-throughput sequencing technology. However, the regulatory roles of most identified miRNAs in swine testicular development or spermatogenesis are poorly understood. In our previous study, ULK2 (uncoordinated-51-like kinase 2) was predicted as a target gene of miR-26a. In this study, we aimed to investigate the role of miR-26a in swine Sertoli cell autophagy. The relative expression of miR-26a and ULK2 levels has a significant negative correlation (R = .5964, p ≤ .01) in nine developmental stages of swine testicular tissue. Dual-luciferase reporter assay results show that miR-26a directly targets the 3'UTR of the ULK2 gene (position 618-624). In addition, both the mRNA and protein expression of ULK2 were downregulated by miR-26a in swine Sertoli cells. These results indicate that miR-26a targets the ULK2 gene and downregulates its expression in swine Sertoli cells. Based on the expression of marker genes (LC3, p62 and Beclin-1), overexpression of miR-26a or knock-down of ULK2 inhibits swine Sertoli cell autophagy. Taken together, these findings demonstrate that miR-26a suppresses autophagy in swine Sertoli cells by targeting ULK2.

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MiR-26a functions oppositely in osteogenic differentiation of BMSCs and ADSCs depending on distinct activation and roles of Wnt and BMP signaling pathway

Cited by 108 publications

References 55 publications

Melatonin protects bone marrow mesenchymal stem cells against iron overload‐induced aberrant differentiation and senescence

Melatonin protects bone marrow mesenchymal stem cells against iron overload‐induced aberrant differentiation and senescence

miR-16-2* Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells

miR‐26a suppresses autophagy in swine Sertoli cells by targeting ULK2

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