Redundant let‐7a suppresses the immunomodulatory properties of BMSCs by inhibiting the Fas/FasL system in osteoporosis

Liao, Li; Yu, Yang; Shao, Bingyi; Su, Xiaoxia; Wang, Han; Kuang, Huijuan; Jing, Huan; Yi, Siyan; Yang, Deqin; Jin, Yan

doi:10.1096/fj.201700885r

Cited by 11 publications

(14 citation statements)

References 51 publications

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“…The let-7a induced by TNF-α in osteoporosis, inhibited the expression of the Fas/FasL system via post-transcriptional regulation. Silencing let-7a expression can recover the immunosuppressive capacity of osteoporotic bone marrow mesenchymal stem cells (BMSCs) [19]. By regulating TGFBR1, the let-7a-5p might inhibit the osteogenic differentiation of BMSCs in postmenopausal osteoporosis (PMOP) mice [20].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Hub Genes and miRNAs in Osteoporosis

Huang

Zhao

et al. 2021

Preprint

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Background and objective: Osteoporosis (OP) is a systemic disease of bone metabolism, characterized by decreasing bone mass, increasing bone microstructure damages and fracture risk. It affects the quality of life of nearly 200 million people worldwide and is a major burden on the public health systems. We want to identify hub genes and miRNAs by the miRNA-mRNA interaction network in osteoporosis disease so that further understand the pathogenesis of this disease.Materials and methods: The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were selected using data of OP patients downloaded from the GEO database (GSE93883, GSE74209 and GSE35959). Gene Ontology (GO) pathway analysis and transcription factor enrichment analysis were used for selecting DEMis, and the target mRNAs of DEMis were filtered by using FunRich. Cytoscape software was used to visualize the network between miRNAs and mRNAs and calculate the hub genes. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the mRNAs in the regulatory network.Results: A total of 17 DEMis and 655 DEMs were selected, from which we reconstructed the miRNA-mRNA network consisting of 6 miRNAs and 37 mRNAs. The top 10 nodes, hsa-let-7a-5p, hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-223-3p, hsa-miR-320c, SLC2A3(Solute Carrier Family 2 Member 3), LBX1(ladybird homeobox 1), HCN2(hyperpolarization-activated cyclic nucleotide-gated ion channel 2), DAB2IP(DAB2 Interacting Protein) and CIC(capicua transcriptional repressor), were identified as important regulators.Conclusions: The study uncovered several important hub genes and miRNAs involved in the pathogenesis of OP, among which, the hsa-let-7a-5p, hsa-miR-92a-3p and hsa-miR-92b-3p may play an important role in osteoporosis, which can help us provide potential therapeutic targets of OP.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Hub Genes and miRNAs in Osteoporosis

Huang

Zhao

et al. 2021

Preprint

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“…We also found that the immunoregulation of BMSCs was affected by the Fas / FasL pathway in osteoporosis. These findings suggest that the pathological condition of the donor may affect the immunosuppressive effects of BMSCs 1,7 . Although recent studies have shown that the recognition of small molecular compounds can counteract inflammatory insults in BMSCs, 8 a pharmacological solution that promotes the immunosuppressive effects of BMSCs derived from inflammatory microenvironment has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

Osthole enhances the immunosuppressive effects of bone marrow‐derived mesenchymal stem cells by promoting the Fas/FasL system

Chen

Yang

et al. 2021

J Cellular Molecular Medi

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Thanks to the advantages of easy harvesting and escape from immune rejection, autologous bone marrow‐derived mesenchymal stem cells (BMSCs) are promising candidates for immunosuppressive therapy against inflammation and autoimmune diseases. However, the therapy is still challenging because the immunomodulatory properties of BMSCs are always impaired by immunopathogenesis in patients. Because of its reliable and extensive biological activities, osthole has received increased clinical attention. In this study, we found that BMSCs derived from osteoporosis donors were ineffective in cell therapy for experimental inflammatory colitis and osteoporosis. In vivo and in vitro tests showed that because of the down‐regulation of Fas and FasL expression, the ability of osteoporotic BMSCs to induce T‐cell apoptosis decreased. Through the application of osthole, we successfully restored the immunosuppressive ability of osteoporotic BMSCs and improved their treatment efficacy in experimental inflammatory colitis and osteoporosis. In addition, we found the immunomodulatory properties of BMSCs were enhanced after osthole pre‐treatment. In this study, our data highlight a new approach of pharmacological modification (ie osthole) to improve the immune regulatory performance of BMSCs from a healthy or inflammatory microenvironment. The development of targeted strategies to enhance immunosuppressive therapy using BMSCs may be significantly improved by these findings.

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“…Bone marrow mesenchymal stem cells (BMSCs) are a type of multipotent progenitor cells and could be differentiated into multiple lineages (Li, Chang, Yeh, & Hu, 2016; Li et al., 2018; Liao et al., 2018). BMSCs undergo differentiation into various cell types, such as osteoblasts, adipocytes, fibroblasts, and chondrocytes (Luo et al., 2019).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol benefits the lineage commitment of bone marrow mesenchymal stem cells into osteoblasts via miR‐320c by targeting Runx2

Zou

et al. 2021

J Tissue Eng Regen Med

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Bone marrow mesenchymal stem cells (BMSCs) are a potential source of osteoblasts and have been widely used in clinical therapies due to their pluripotency. Recent publications have found that resveratrol (RSVL) played a crucial role in the proliferation and differentiation of BMSCs; however, the underlying molecular mechanism of RSVL‐induced BMSCs osteogenic differentiation needs to be fully elucidated. The objective of this study was to explore functions of miRNAs in the RSVL‐treated BMSCs and its effects on the differentiation potentials of BMSCs. The findings demonstrated that RSVL enhanced the osteogenesis and suppressed the adipogenesis of BMSCs in a dose‐dependent manner. Besides, a novel regulatory axis containing miR‐320c, and its target Runx2 was found during the differentiation process of BMSCs under RSVL treatment. Increase of miR‐320c reduced the osteogenic potential of BMSCs, while knockdown of miR‐320c played a positive role in the osteogenesis of BMSCs. In contrast, overexpression of miR‐320c accelerated the adipogenic differentiation, while knockdown of miR‐320c restrained the adipogenic differentiation of BMSCs. The results confirmed that Runx2 might be the direct target of miR‐320c in RSVL‐promoted osteogenic differentiation of BMSCs. This study revealed that RSVL might be used for the treatment of bone loss related diseases and miR‐320c could be regarded as a novel and potential target to regulate the biological functions of BMSCs.

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Redundant let‐7a suppresses the immunomodulatory properties of BMSCs by inhibiting the Fas/FasL system in osteoporosis

Cited by 11 publications

References 51 publications

Integrated Analysis of Hub Genes and miRNAs in Osteoporosis

Integrated Analysis of Hub Genes and miRNAs in Osteoporosis

Osthole enhances the immunosuppressive effects of bone marrow‐derived mesenchymal stem cells by promoting the Fas/FasL system

Resveratrol benefits the lineage commitment of bone marrow mesenchymal stem cells into osteoblasts via miR‐320c by targeting Runx2

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