microRNA Regulation of Skeletal Development

Sera, Steven R; Nieden, Nicole I. zur

doi:10.1007/s11914-017-0379-7

Cited by 35 publications

(19 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, miR-21 has also been reported as a mediator of angiogenesis and wound healing 50 , and this expression pattern was also previously described in bone tissue of union and non-union fracture animal models 21 , 22 . Also, rat MSC overexpressing miR-21 induced better fracture healing, with a recent review suggesting that the pro-osteogenic role of miR-21 may be through the indirect regulation of Col1a1 , and that it is induced by the TGF-β and BMP pathways 51 . Moreover, as mentioned above, a clinical study comparing circulating miRNAs in serum of patients with osteoporotic fractures with non-osteoporotic fracture patients revealed a significant up-regulation of miR-21 24 ; however, this study did not focus on the comparison with the plasma miRNA profile upon fracture in healthy subjects.…”

Section: Discussionmentioning

confidence: 98%

Profiling the circulating miRnome reveals a temporal regulation of the bone injury response

Silva¹,

Almeida²,

Teixeira³

et al. 2018

Theranostics

View full text Add to dashboard Cite

Bone injury healing is an orchestrated process that starts with an inflammatory phase followed by repair and remodelling of the bone defect. The initial inflammation is characterized by local changes in immune cell populations and molecular mediators, including microRNAs (miRNAs). However, the systemic response to bone injury remains largely uncharacterized. Thus, this study aimed to profile the changes in the plasma miRnome after bone injury and determine its biological implications.Methods: A rat model of femoral bone defect was used, and animals were evaluated at days 3 and 14 after injury. Non-operated (NO) and sham operated animals were used as controls. Blood and spleen were collected and peripheral blood mononuclear cells (PBMC) and plasma were separated. Plasma miRnome was determined by RT-qPCR array and bioinformatics Ingenuity pathway analysis (IPA) was performed. Proliferation of bone marrow mesenchymal stem/stromal cells (MSC) was evaluated by Ki67 staining and high-throughput cell imaging. Candidate miRNAs were evaluated in splenocytes by RT-qPCR, and proteins found in the IPA analysis were analysed in splenocytes and PBMC by Western blot.Results: Bone injury resulted in timely controlled changes to the miRNA expression profile in plasma. At day 3 there was a major down-regulation of miRNA levels, which was partially recovered by day 14 post-injury. Interestingly, bone injury led to a significant up-regulation of let-7a, let-7d and miR-21 in plasma and splenocytes at day 14 relative to day 3 after bone injury, but not in sham operated animals. IPA predicted that most miRNAs temporally affected were involved in cellular development, proliferation and movement. MSC proliferation was analysed and found significantly increased in response to plasma of animals days 3 and 14 post-injury, but not from NO animals. Moreover, IPA predicted that miRNA processing proteins Ago2 and Dicer were specifically inhibited at day 3 post-injury, with Ago2 becoming activated at day 14. Protein levels of Ago2 and Dicer in splenocytes were increased at day 14 relative to day 3 post-bone injury and NO animals, while in PBMC, levels were reduced at day 3 (albeit Dicer was not significant) and remained low at day 14. Ephrin receptor B6 followed the same tendency as Ago2 and Dicer, while Smad2/3 was significantly decreased in splenocytes from day 14 relative to NO and day 3 post-bone injury animals.Conclusion: Results show a systemic miRNA response to bone injury that is regulated in time and is related to inflammation resolution and the start of bone repair/regeneration, unravelling candidate miRNAs to be used as biomarkers in the monitoring of healthy bone healing and as therapeutic targets for the development of improved bone regeneration therapies.

show abstract

Section: Discussionmentioning

confidence: 98%

Profiling the circulating miRnome reveals a temporal regulation of the bone injury response

Silva¹,

Almeida²,

Teixeira³

et al. 2018

Theranostics

View full text Add to dashboard Cite

show abstract

“…Among ncRNAs, miRNAs have been most extensively studied in relation to bone and cartilage diseases. More than 35 miRNAs modulate the differentiation of osteoblast precursors in vitro, through various mechanisms, including targeting master regulators such as RUNX2 (see recent reviews) . A few of them have demonstrated effects on bone in animal models in vivo and may be involved in osteoclast‐osteoblast communication.…”

Section: Non‐coding Rnas In Skeletal Disordersmentioning

confidence: 99%

Role of Epigenomics in Bone and Cartilage Disease

Meurs

Boer

López-Delgado

et al. 2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Phenotypic variation in skeletal traits and diseases is the product of genetic and environmental factors. Epigenetic mechanisms include information-containing factors, other than DNA sequence, that cause stable changes in gene expression and are maintained during cell divisions. They represent a link between environmental influences, genome features, and the resulting phenotype. The main epigenetic factors are DNA methylation, posttranslational changes of histones, and higher-order chromatin structure. Sometimes non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are also included in the broad term of epigenetic factors. There is rapidly expanding experimental evidence for a role of epigenetic factors in the differentiation of bone cells and the pathogenesis of skeletal disorders, such as osteoporosis and osteoarthritis. However, different from genetic factors, epigenetic signatures are cell-and tissue-specific and can change with time. Thus, elucidating their role has particular difficulties, especially in human studies. Nevertheless, epigenomewide association studies are beginning to disclose some disease-specific patterns that help to understand skeletal cell biology and may lead to development of new epigenetic-based biomarkers, as well as new drug targets useful for treating diffuse and localized disorders. Here we provide an overview and update of recent advances on the role of epigenomics in bone and cartilage diseases.Besides chromatin-related marks and structure, non-coding RNAs (ncRNAs) are also frequently included among the mechanisms of epigenetic control. (8) They are classified as small RNAs (<200 nucleotides) and long RNAs (>200 nucleotides). The best-known subset of small RNAs are microRNAs (miRNAs, 18 to 25 nucleotides), which inhibit protein synthesis by binding to the 3 0 -untranslated region of target mRNAs. Long non-coding RNAs (lncRNAs) modulate the activity of both nearby genes and distant genes by a variety of mechanisms. For instance, they often serve as scaffolds for transcription factors and other molecules involved in initiation of transcription, including Box 1. Epigenomics-Related TermsChromatin: The complex of DNA and its packaging molecules. The core of the chromatin is the nucleosome, which consists of an octamer of 4 histones around which 147 bp of DNA is wrapped around.Chromosome conformation capture and Hi-C: Techniques used to map the spatial (3D) organization of the chromatin in the nucleus. Chromosome conformation capture (3C) quantifies the number of interactions between a given loci and the rest of the genome. In Hi-C, all genomic interaction between all genomic regions are quantified.CTCF: CCCTC-binding factor, highly conserved zinc finger protein involved in diverse genomic regulatory functions, including transcriptional activation/repression, insulation, imprinting, and X-chromosome inactivation, through mediating the formation of chromatin loops. DNA methyl-transferases (DNMTs): Family of enzymes responsible for the methylation of DNA. DNMT1...

show abstract

“…Mechanosensitive miRNAs temporally changed with mechanical use/disuse, and played important roles in osteogenic differentiation under different mechanical conditions. Without mechanical stimuli, the gain or loss of function of the mechanosensitive microRNAs still affects many bio-active molecules indispensable to the regulation of osteogenic differentiation in nature [ 21 , 61 , 62 , 63 ].…”

Section: Mechanosensitive Mirnas and Osteogenic Differentiationmentioning

confidence: 99%

Mechanosensitive miRNAs and Bone Formation

Chen

Zhang

Liang

et al. 2017

IJMS

View full text Add to dashboard Cite

Mechanical stimuli are required for the maintenance of skeletal integrity and bone mass. An increasing amount of evidence indicates that multiple regulators (e.g., hormone, cytoskeleton proteins and signaling pathways) are involved in the mechanical stimuli modulating the activities of osteogenic cells and the process of bone formation. Significantly, recent studies have showed that several microRNAs (miRNAs) were sensitive to various mechanical stimuli and played a crucial role in osteogenic differentiation and bone formation. However, the functional roles and further mechanisms of mechanosensitive miRNAs in bone formation are not yet completely understood. This review highlights the roles of mechanosensitive miRNAs in osteogenic differentiation and bone formation and underlines their potential therapeutic application for bone loss induced by the altering of mechanical stimuli.

show abstract

microRNA Regulation of Skeletal Development

Cited by 35 publications

References 148 publications

Profiling the circulating miRnome reveals a temporal regulation of the bone injury response

Profiling the circulating miRnome reveals a temporal regulation of the bone injury response

Role of Epigenomics in Bone and Cartilage Disease

Mechanosensitive miRNAs and Bone Formation

Contact Info

Product

Resources

About