Transient exposure to miR‐203 enhances the differentiation capacity of established pluripotent stem cells

Salazar, María; Trakala, Marianna; Álvarez-Fernández, Mónica; Valdés-Mora, Fátima; Zhong, Cuiqing; Muñoz, Jaime; Yu, Yang; Graña‐Castro, Osvaldo; Serrano, Rosa; Zapatero-Solana, Elisabet; Abad, María; Bueno, María José Sánchez; Cedrón, Marta Gómez de; Fernández‐Piqueras, José; Serrano, Manuel; Blasco, Marı́a A.; Wang, Dazhi; Clark, Susan J.; Izpisúa-Belmonte, Juan Carlos; Ortega, Sagrario; Malumbres, Marcos

doi:10.15252/embj.2019104324

Cited by 17 publications

(24 citation statements)

References 66 publications

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“…There are 43 exosomal miRNAs highly expressed in MC3T3-E1 cells during the osteogenesis process, such as miR-30d-5p and miR-133b-3p [ 44 , 45 ]. Moreover, miR-135b , miR-203 , and miR-299-5p are upregulated in human-BMSCs derived exosomes during osteogenesis [ 46 – 48 ]. Thus, in the present study, we aimed to identify the differences in exosomal miRNAs between N-Exos and DM-Exos.…”

Section: Discussionmentioning

confidence: 99%

Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats

et al. 2022

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Background Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats

et al. 2022

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“…There are 43 exosomal miRNAs highly expressed in MC3T3-E1 cells during the osteogenesis process, such as miR-30d-5p and miR-133b-3p (Li et al, 2008;Zhang et al, 2011). Moreover, miR-135b, miR-203, and miR-299-5p are upregulated in human-BMSCs derived exosomes during osteogenesis (Panganiban et al, 2016;Salazar-Roa et al, 2020;Schaap-Oziemlak et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

BMSC-Derived Exosomal MiRNAs Can Modulate Bone Restoration in Diabetic Rats with Femoral Defects

Wang

Liu

Tang

et al. 2021

Preprint

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The exosomal miRNAs of BMSCs participate in hyperglycemia induced poor healing of bone defects. Here, we demonstrate that exosomes derived from BMSCs harvested from diabetes mellitus(DM) rats suppressed bone formation when administered to normal rats with bone defects. Using high-throughput sequencing analysis of microRNA molecules, high miR-140-3p levels were expressed in exosomes released by N-BMSCs. Using TargetScan software and luciferase activity assays, plxnb1 was identified as the downstream molecular target of exosomal miR-140-3p that regulated osteogenesis. Transplantation of exosomes that overexpressed miR-140-3p into DM rats promoted the restoration of bone defects. Furthermore, miR-140-3p significantly promoted the differentiation of DM-BMSCs into osteoblasts and inhibited the expression p-RohA and p-ROCK in the plexin B1 signaling pathway. Taken together, these observations suggest that DM decreases the levels of exosomal miR-140-3p, which impedes bone formation and the differentiation of BMSCs. MiR-140-3p may represent a potential therapeutic target for DM related to abnormal bone metabolism.

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“…In addition to miR-1 and miR-499, overexpression of miR-203 improves efficient differentiation and maturation to cardiomyocytes by repression of DNA methyltransferase 3a/b (Dnmt3a/b) in mouse iPSCs ( Salazar-Roa et al, 2020 ). miR-322 and miR-503 clusters have shown that participate in the specification into cardiomyocyte progenitors of the mesodermal cells by the repression of CUGBP Elav-like family member (Celf) family proteins ( Shen et al, 2016 ).…”

Section: Part 2: Mirnas and Cardiac Regenerationmentioning

confidence: 99%

Non-coding RNAs in Cardiac Regeneration

Yuan

Krishnan

2021

Front. Physiol.

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The adult heart has a limited capacity to replace or regenerate damaged cardiac tissue following severe myocardial injury. Thus, therapies facilitating the induction of cardiac regeneration holds great promise for the treatment of end-stage heart failure, and for pathologies invoking severe cardiac dysfunction as a result of cardiomyocyte death. Recently, a number of studies have demonstrated that cardiac regeneration can be achieved through modulation and/or reprogramming of cardiomyocyte proliferation, differentiation, and survival signaling. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are reported to play critical roles in regulating key aspects of cardiomyocyte physiologic and pathologic signaling, including the regulation of cardiac regeneration both in vitro and in vivo. In this review, we will explore and detail the current understanding of ncRNA function in cardiac regeneration, and highlight established and novel strategies for the treatment of heart failure through modulation of ncRNAs-driven cardiac regeneration.

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Transient exposure to miR‐203 enhances the differentiation capacity of established pluripotent stem cells

Cited by 17 publications

References 66 publications

Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats

Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats

BMSC-Derived Exosomal MiRNAs Can Modulate Bone Restoration in Diabetic Rats with Femoral Defects

Non-coding RNAs in Cardiac Regeneration

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