Souad Daamouch, Andreas Diendorfer, Matthias Hackl, Gabriele Christoffel, Lorenz C Hofbauer, Martina Rauner
{"title":"Exploratory miRNA profiling from serum and bone tissue of mice with T1D-induced bone loss.","authors":"Souad Daamouch, Andreas Diendorfer, Matthias Hackl, Gabriele Christoffel, Lorenz C Hofbauer, Martina Rauner","doi":"10.3389/fendo.2024.1477257","DOIUrl":null,"url":null,"abstract":"<p><p>Type 1 diabetes (T1D) represents a significant health burden worldwide, with associated complications including bone fragility. Current clinical methods and biomarkers for assessing bone health and predicting fracture risk in T1D are limited and lack accuracy. MicroRNAs (miRNAs) have emerged as potential biomarkers for predicting T1D-induced bone loss, although comprehensive profiling studies are lacking. Previous investigations have indicated a link between dysregulated miRNA expression levels and impaired bone health in T1D. Therefore, in this study, we explored differential miRNA expression levels in serum and bone tissue of mice with T1D-induced bone loss using Next Generation Sequencing (NGS). T1D was induced using streptozotocin in male wild-type mice. Serum and bone tissues were analyzed at 14 weeks of age, following the prior characterization of bone loss in this mouse model. MiRNA profiling was conducted using two-independent NGS analyses and validated through quantitative RT-PCR. NGS profiling identified differential expression of miRNAs in serum and bone tissue of T1D mice compared to controls. The first NGS analysis revealed 24 differentially expressed miRNAs in serum and 13 in bone tissue. Especially, miR-136-3p was consistently downregulated in both serum and bone tissue. However, the second NGS analysis presented a distinct set of dysregulated miRNAs, with miR-206-3p overlapping in both tissues but exhibiting differential expression patterns. Surprisingly, miR-144-5p, miR-19a-3p, and miR-21a-5p displayed contrasting regulatory patterns between NGS and qPCR analyses. Finally, gene network analysis identified associations between dysregulated miRNAs and pathways involved in bone physiology, including TGF-beta, PI3-Akt signaling, and osteoclast differentiation in humans. In conclusion, our study offers initial insights into dysregulated miRNAs associated with T1D-induced bone loss, but also highlights the lack of consistency in the results obtained from miRNA sequencing in different cohorts. Thus, further investigation is needed to better understand the complexities of miRNA analyses before they can be established as reproducible biomarkers for predicting bone health in T1D.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"15 ","pages":"1477257"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703745/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fendo.2024.1477257","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Type 1 diabetes (T1D) represents a significant health burden worldwide, with associated complications including bone fragility. Current clinical methods and biomarkers for assessing bone health and predicting fracture risk in T1D are limited and lack accuracy. MicroRNAs (miRNAs) have emerged as potential biomarkers for predicting T1D-induced bone loss, although comprehensive profiling studies are lacking. Previous investigations have indicated a link between dysregulated miRNA expression levels and impaired bone health in T1D. Therefore, in this study, we explored differential miRNA expression levels in serum and bone tissue of mice with T1D-induced bone loss using Next Generation Sequencing (NGS). T1D was induced using streptozotocin in male wild-type mice. Serum and bone tissues were analyzed at 14 weeks of age, following the prior characterization of bone loss in this mouse model. MiRNA profiling was conducted using two-independent NGS analyses and validated through quantitative RT-PCR. NGS profiling identified differential expression of miRNAs in serum and bone tissue of T1D mice compared to controls. The first NGS analysis revealed 24 differentially expressed miRNAs in serum and 13 in bone tissue. Especially, miR-136-3p was consistently downregulated in both serum and bone tissue. However, the second NGS analysis presented a distinct set of dysregulated miRNAs, with miR-206-3p overlapping in both tissues but exhibiting differential expression patterns. Surprisingly, miR-144-5p, miR-19a-3p, and miR-21a-5p displayed contrasting regulatory patterns between NGS and qPCR analyses. Finally, gene network analysis identified associations between dysregulated miRNAs and pathways involved in bone physiology, including TGF-beta, PI3-Akt signaling, and osteoclast differentiation in humans. In conclusion, our study offers initial insights into dysregulated miRNAs associated with T1D-induced bone loss, but also highlights the lack of consistency in the results obtained from miRNA sequencing in different cohorts. Thus, further investigation is needed to better understand the complexities of miRNA analyses before they can be established as reproducible biomarkers for predicting bone health in T1D.
期刊介绍:
Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series.
In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology.
Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.