Overexpressed miR-145 inhibits osteoclastogenesis in RANKL-induced bone marrow-derived macrophages and ovariectomized mice by regulation of Smad3

Yu, Fangyuan; Xie, Congqin; Sun, Jitong; Peng, Wei; Huang, Xunwu

doi:10.1016/j.lfs.2018.03.042

Cited by 45 publications

(30 citation statements)

References 36 publications

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“…This suggested that SMAD3 may differentially affect osteoblast differentiation depending upon the differentiation stage (38). microRNA-145 was demonstrated to epi-genetically regulate osteogenesis by decreasing SMAD3 expression (62). It is reasonable to suggest that osteoblast differentiation, epigenetic regulation and SMAD3 expression are associated.…”

Section: Discussionmentioning

confidence: 98%

Dynamic expression of SMAD3 is critical in�osteoblast differentiation of PDMCs

et al. 2018

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Human pluripotent stem cells have the potential assist in the identification of genes involved in mammalian development. The human placenta is considered a repository of stem cells, termed placenta-derived multipotent cells (PDMCs), which are able to differentiate into cells with an osteoblastic phenotype. This plasticity of PDMCs maybe applied clinically to the understanding of osteogenesis and osteoporosis. In the presentstudy, osteoblasts were generated by culturing PDMCs in osteogenic medium. Reverse transcription quantitative polymerase chain reactionand the degree of osteoblast calcification were used to evaluate the efficacy of osteogenesis. The results suggestedthat the expression of mothers against decapentaplegic homolog 3 (SMAD3) increased in the initial stages of osteogenic differentiation but decreased in the later stages. However, osteogenesis was inhibitedwhen the PDMCs overexpressed SMAD3 throughout the differentiation period. In addition, the rate of osteogenic differentiation was decreased when SMAD3 signaling was impaired. In conclusion, SMAD3 serves an important role in osteoblast differentiation and bone formation in a time-dependent manner. The data from the present study indicate that arapid increase in SMAD3 expression is crucial for osteogenesis and suggest a role for PDMCs in the treatment of patients with osteoporosis.

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Section: Discussionmentioning

confidence: 98%

Dynamic expression of SMAD3 is critical in�osteoblast differentiation of PDMCs

et al. 2018

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“…Western blotting assay was determined as described previously. 22 The primary antibody for Gas6 was purchased from Abcam (Cambridge, UK…”

Section: Western Blottingmentioning

confidence: 99%

Celastrol mitigates high glucose‐induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR‐345‐5p/growth arrest‐specific 6

Cao

Zhang

et al. 2020

The Journal of Gene Medicine

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Background Celastrol (Cel) has been corroborated as an anti‐inflammatory and anti‐apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)‐induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG‐stimulated cardiomyocyte injury via regulating the miR‐345‐5p/growth arrest‐specific 6 (Gas6) signaling pathway. Methods Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit‐8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase‐polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR‐345‐5p. Results The present study confirmed the inhibitory effects of Cel in HG‐induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG‐induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl‐2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG‐triggered repression of Gas6 protein expression, and Gas6 loss‐of‐function accelerated HG‐induced cardiomyocyte apoptosis. HG‐triggered up‐regulation of miR‐345‐5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR‐345‐5p. Transfection with miR‐345‐5p inhibitors restrained HG‐induced release of pro‐inflammatory cytokines and cell apoptosis. Conclusions The findings of the present study demonstrate that Cel administration antagonized HG‐induced cardiomyocyte apoptosis and inflammation through up‐regulating Gas6 expression by restraining miR‐345‐5p.

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“…Of all the predicted target genes, we found that Smad3, Cbfb, Smad5, Ctnnbip1, which was highlighted with blue colour in Figure6 A, are involved in osteoblast differentiation. Then we explore Smad3 and Cbfb, which had been veri ed as the target genes of miR-145a [22][23][24], given its reported role in altering bone formation and metabolism in other studies [25,26]. However, we cannot conclude that Smad3 is the target gene of miR-145a because the overexpression of miR-145a did not affect the mRNA and protein level of Smad3 in C3H10T1/2 cells (Supplemental Figure S5 A, B).…”

Section: Mir-145a Inhibited Mscs Osteogenesis By Targeting Cbfbmentioning

confidence: 98%

The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

Xia

Jiang

Wang

et al. 2020

Preprint

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Background: The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is diminished. However, little is known about the mechanisms. p53 not only regulates cellular senescence but also, as a negative regulator, is involved in bone formation. This study investigated the molecular mechanism of p53 in cellular senescence and osteogenesis.Methods: The expression of p53 and its downstream gene p21 were measured during cellular senescence and osteogenesis differentiation of primary bone marrow MSCs. Then miR-145a was picked out from those p53-induced miRNAs as its expression change in bone marrow MSCs senescence and osteogenesis induced by H2O2 and BMP-9, respectively. The function of p53 induced miR-145a was analyzed by transfected with miRNA mimic in osteogenic differentiation of MSCs. Western blot and luciferase reporter assay were used for validating the target of miR-145a. Results: p53, its downstream effector p21, and p53-induced miR-145a were significantly upregulated during primary MSCs senescence and osteogenesis. Overexpression of miR-145a promoted cellular senescence and inhibited osteogenic differentiation of MSCs. p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a on osteogenesis.Conclusions: p53-induced miR-145a functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel pathway p53/miR-145a/Cbfb in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.

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Overexpressed miR-145 inhibits osteoclastogenesis in RANKL-induced bone marrow-derived macrophages and ovariectomized mice by regulation of Smad3

Cited by 45 publications

References 36 publications

Dynamic expression of SMAD3 is critical in�osteoblast differentiation of PDMCs

Dynamic expression of SMAD3 is critical in�osteoblast differentiation of PDMCs

Celastrol mitigates high glucose‐induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR‐345‐5p/growth arrest‐specific 6

The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

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