Altered expression of microRNA during fracture healing in diabetic rats

Takahara, Shunsuke; Lee, S. Y.; Igarashi, Takashi; Oe, Keisuke; Fukui, Tomoaki; Okumachi, Etsuko; Waki, Takahiro; Arakura, Michio; Sakai, Yoshitada; Nishida, Kotaro; Kuroda, Ryosuke; Niikura, Takahiro

doi:10.1302/2046-3758.72.bjr-2017-0082.r1

Cited by 29 publications

(36 citation statements)

References 34 publications

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“…mirnas have previously attracted attention as potential biomarkers of BN (36)(37)(38)(39), warranting the identification of deMs in Bn patient bone tissue samples. The present study revealed that mir-1225-5p is highly expressed in Bn tissues.…”

Section: Discussionmentioning

confidence: 99%

“…elevated plasma mir-339-5p levels have previously been identified as a biomarker of lung adenocarcinoma (39) and linked to increased activation of the protein B-cell lymphoma 6 (41), whereas upregulation of the resulting protein suppresses PRCP expression (42,43). Consistent with these findings, the present study revealed that mir-339-5p was upregulated in Fc, fold-change; mirna, microrna.…”

Section: Discussionmentioning

confidence: 99%

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Identification of key microRNAs and target genes for the diagnosis of bone nonunion

et al. 2020

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a number of recent studies have highlighted the causes of bone nonunion (Bn), however, the rate of Bn incidence continues to rise and available therapeutic options to treat this condition remain limited. Thus, to prevent disease progression and improve patient prognosis, it is vital that BN, or the risk thereof, be accurately identified in a timely manner. in the present study, bioinformatics analyses were used to screen for the differentially expressed genes (deGs) and differentially expressed mirnas (deMs) between patients with Bn and those with bone union, using data from the Gene expression omnibus database. Furthermore, clinical samples were collected and analyzed by reverse transcription-quantitative Pcr and western blotting. In vitro and in vivo experiments were carried out to confirm the relationship between Bn and the deGs of interest, in addition to being used to explore the underlying molecular mechanism of Bn. Functional enrichment analysis of the downregulated deGs revealed them to be enriched for genes associated with 'ecM-receptor interactions', 'focal adhesion', 'and the calcium signaling pathway'. When comparing deM target genes with these DEGs, nine DEGs were identified as putative deM targets, where hsa-microrna (mir)-1225-5p-ccnl2, hsa-mir-339-5p-PrcP, and hsa-mir-193a-3p-mitogen-activated protein kinase 10 (MaPK10) were the only three pairs which were associated with decreased gene expression levels. Furthermore, hsa-mir-193a-3p was demonstrated to induce Bn by targeting MaPK10. collectively, the results of the present study suggest that hsa-mir-193a-3p may be a viable biomarker of Bn.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of key microRNAs and target genes for the diagnosis of bone nonunion

et al. 2020

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“…Recently, investigators designed a new scoring system to assess the miRNA contribution to impaired fracture healing, and 11 miRNAs were identified to impairing fracture healing in aged female mice [14] . The expression of five miRNAs (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p and miR-222-3p) is altered in diabetic mice with impaired fracture healing when compared to normal mice [15] . As SPC3649, the first miRNA-targeting drug for the treatment of hepatitis C virus infection, is being investigated in clinical trials [16] , we speculate that promoting or inhibiting miRNA function is a potential therapy for nonunion.…”

Section: Genetic Factorsmentioning

confidence: 99%

Molecular pathogenesis of fracture nonunion

Ding

Lin

Gan

et al. 2018

Journal of Orthopaedic Translation

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Fracture nonunion, a serious bone fracture complication, remains a challenge in clinical practice. Although the molecular pathogenesis of nonunion remains unclear, a better understanding may provide better approaches for its prevention, diagnosis and treatment at the molecular level. This review tries to summarise the progress made in studies of the pathogenesis of fracture nonunion. We discuss the evidence supporting the concept that the development of nonunion is related to genetic factors. The importance of several cytokines that regulate fracture healing in the pathogenesis of nonunion, such as tumour necrosis factor-α, interleukin-6, bone morphogenetic proteins, insulin-like growth factors, matrix metalloproteinases and vascular endothelial growth factor, has been proven in vitro, in animals and in humans. Nitric oxide and the Wnt signalling pathway also play important roles in the development of nonunion. We present potential strategies for the prevention, diagnosis and treatment of nonunion, and the interaction between genetic alteration and abnormal cytokine expression warrants further investigation.The translational potential of this articleA better understanding of nonunion molecular pathogenesis may provide better approaches for its prevention, diagnosis and treatment in clinical practice.

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“…miR-148a and miR-21-5p target pivotal genes involved in bone development, modeling, and remodeling (e.g., wingless-type MMTV integration site family, member 1 (WNT1), and transforming growth factor-β 2 (TGF-β2)), thus suggesting that miR-148a and miR-21-5p serve as contributing factors to bone fragility or as potential biomarkers of bone metabolic alterations in patients with type 1 DM [21]. However, only a few studies have shown direct roles for miRNAs in impaired fracture healing in patients with DM or in animal models of DM [22].…”

Section: Introductionmentioning

confidence: 99%

Altered microRNA profile during fracture healing in rats with diabetes

et al. 2020

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Background: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression. There is increasing evidence that some miRNAs are involved in the pathology of diabetes mellitus (DM) and its complications. We hypothesized that the functions of certain miRNAs and the changes in their patterns of expression may contribute to the pathogenesis of impaired fractures due to DM. Methods: In this study, 108 male Sprague-Dawley rats were divided into DM and control groups. DM rats were created by a single intravenous injection of streptozotocin. Closed transverse femoral shaft fractures were created in both groups. On post-fracture days 5, 7, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was conducted with miRNA samples from each group on post-fracture days 5 and 11. The microarray findings were validated by real-time polymerase chain reaction (PCR) analysis at each time point. Results: Microarray analysis revealed that, on days 5 and 11, 368 and 207 miRNAs, respectively, were upregulated in the DM group, compared with the control group. The top four miRNAs on day 5 were miR-339-3p, miR451-5p, miR-532-5p, and miR-551b-3p. The top four miRNAs on day 11 were miR-221-3p, miR376a-3p, miR-379-3p, and miR-379-5p. Among these miRNAs, miR-221-3p, miR-339-3p, miR-376a-3p, miR-379-5p, and miR-451-5p were validated by real-time PCR analysis. Furthermore, PCR analysis revealed that these five miRNAs were differentially expressed with dynamic expression patterns during fracture healing in the DM group, compared with the control group. Conclusions: Our findings will aid in understanding the pathology of impaired fracture healing in DM and may support the development of molecular therapies using miRNAs for the treatment of impaired fracture healing in patients with DM.

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Altered expression of microRNA during fracture healing in diabetic rats

Cited by 29 publications

References 34 publications

Identification of key microRNAs and target genes for the diagnosis of bone nonunion

Identification of key microRNAs and target genes for the diagnosis of bone nonunion

Molecular pathogenesis of fracture nonunion

Altered microRNA profile during fracture healing in rats with diabetes

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