The role of miR-31-modified adipose tissue-derived stem cells in repairing rat critical-sized calvarial defects

Deng, Yuan; Zhou, Huifang; Zou, Duohong; Xie, Qing; Bi, Xiaoping; Gu, Ping; Fan, Xianqun

doi:10.1016/j.biomaterials.2013.05.042

Cited by 116 publications

(116 citation statements)

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“…The increased level of miR‐31a‐5p was further confirmed by the estrogen‐deficient aging model, replicative aging model and human aging model. SATB2 is a target gene of miR‐31a‐5p, which has been proven by some prior studies (Aprelikova et al., 2010; Deng, Weng et al., 2013; Deng, Zhou et al., 2013). Our previous investigation has demonstrated that SATB2, as a transcriptional regulator, functions broadly (Dong et al., 2015) and is involved in osteogenic differentiation in age‐related BMSCs (Strickland, Wasserman, Giassi, Djordjevic, & Parra‐Herran, 2016; Zhou et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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“…In comparison with retroviruses, lesser insertional mutagenesis risks are reported with the use of lentiviruses, [44] thus perhaps encouraging recent developments with lentiviral engineering of cells prior to seeding onto biomaterial scaffolds. [45][46][47] ADVs and AAVs delivering miRNAs are less explored in biomaterial-based RM approaches, although their use in traditional in vitro transductions with miRNA-expressing cassettes has been discussed in other reviews. [48] Figure 3.…”

Section: Viral Vectorsmentioning

confidence: 99%

“…[107] Many distinct scaffold types have been tuned to serve the purpose of miRNA delivery, including several hydrogels, [58,92,106,[108][109][110][111][112][113][114] electrospun fibers, [63,[115][116][117][118] and more prolifically porous or spongy scaffolds. [46,47,50,54,55,96,112,[119][120][121][122][123][124][125][126][127][128][129][130] Before reviewing the details of their applications, summarized in Table 2 and described further in the next section, we will discuss the key characteristics making these materials amenable to miRNA delivery. First very general qualities must be fulfilled: biocompatibility, bioresorbability and ease of fabrication.…”

Section: Scaffolds For Microrna Deliverymentioning

confidence: 99%

“…CaPs exist in forms of different stoichiometric proportion of calcium to phosphate; this includes brushite, tricalcium phosphate (TCP), and hydroxyapatite (HA), the mineral component found in teeth and bone. [140] β-TCP scaffolds were used by Deng et al in preclinical studies of lentiviral miR-31 inhibition, [45,120] and HA/TCP scaffolds were utilized, in combination with Lipofectamine 2000, by Eskildsen et al to deliver miR-138 inhibitors in vitro, [54] and more recently by Wang and co-workers to deliver miR-26a mimics in vivo. [55] Similarly, nHA/PCL and carboxy-methyl-cellulose/zinc-doped nHA composite scaffolds have been combined with Lipofectamine 2000 and X-treme Gene transfection reagent respectively.…”

Section: Scaffolds For Microrna Deliverymentioning

confidence: 99%

“…Finally, Zhang et al [63] importantly demonstrated that miR-26a regulates osteoblast function through targeting glycogen synthase kinase-3beta (GSK-3beta), a gene known to improve bone mass and increase the mineral apposition rate and bone mineral density (BMD) when inhibited in OVX mice. [151] Deng et al [46,120,121] have focused on the assessment of scaffold-mediated miR-31 delivery in various different cells, scaffolds and defect models. Their first study on the evaluation of ASCs combined with lentivirus-miR-31 loaded β-TCP scaffolds [120] showed that miR-31-knockdown ASCs significantly improved bone regeneration in vivo.…”

Section: Osteogenesis and Bone Repairmentioning

confidence: 99%

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Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Curtin

Castaño

O’Brien

2017

Adv Healthcare Materials

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The field of "regenerative medicine" (RM) was conceptually developed to aid the body's natural capacity to self-repair, a capacity which is impaired with age and in cases of disease or injury. [1] RM is a vast and multifaceted area of medicine, often microRNA-based therapies are an advantageous strategy with applications in both regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an evolutionary conserved class of small RNA molecules that modulate up to one third of the human nonprotein coding genome. Thus, synthetic miRNA activators and inhibitors hold immense potential to finely balance gene expression and reestablish tissue health. Ongoing industrysponsored clinical trials inspire a new miRNA therapeutics era, but progress largely relies on the development of safe and efficient delivery systems. The emerging application of biomaterial scaffolds for this purpose offers spatiotemporal control and circumvents biological and mechanical barriers that impede successful miRNA delivery. The nascent research in scaffold-mediated miRNA therapies translates know-how learnt from studies in antitumoral and genetic disorders as well as work on plasmid (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress report, the state of the art methods of regulating miRNAs are reviewed. Relevant miRNA delivery vectors and scaffold systems applied to-date for RM and cancer treatment applications are discussed, as well as the challenges involved in their design. Overall, this progress report demonstrates the opportunity that exists for the application of miRNA-activated scaffolds in the future of RM and cancer treatments.Regenerative Medicine

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Cartilage Tissue Engineering: Recent Advances and Perspectives from Gene Regulation/Therapy

2015

Adv Healthcare Materials

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Diseases in articular cartilages affect millions of people. Despite the relatively simple biochemical and cellular composition of articular cartilages, the self-repair ability of cartilage is limited. Successful cartilage tissue engineering requires intricately coordinated interactions between matrerials, cells, biological factors, and phycial/mechanical factors, and still faces a multitude of challenges. This article presents an overview of the cartilage biology, current treatments, recent advances in the materials, biological factors, and cells used in cartilage tissue engineering/regeneration, with strong emphasis on the perspectives of gene regulation (e.g., microRNA) and gene therapy.

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The role of miR-31-modified adipose tissue-derived stem cells in repairing rat critical-sized calvarial defects

Cited by 116 publications

References 50 publications

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

Scaffold‐Based microRNA Therapies in Regenerative Medicine and Cancer

Cartilage Tissue Engineering: Recent Advances and Perspectives from Gene Regulation/Therapy

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