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Projects / Programmes source: ARIS

Micro RNA – new diagnostic and therapeutic targerts in osteoporosis

Research activity

Code Science Field Subfield
3.07.00  Medical sciences  Metabolic and hormonal disorders   

Code Science Field
B580  Biomedical sciences  Skeleton, muscle system, rheumatology locomotion 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
osteoporosis, microRNA, whole-genome sequencing, genetic background, diagnostic marker, functional study, bone, osteoblast, plasma
Evaluation (rules)
source: COBISS
Researchers (10)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  26227  Manja Cedilnik    Technical associate  2013 
2.  19380  PhD Radko Komadina  Neurobiology  Researcher  2013 - 2016  486 
3.  19649  PhD Marija Nika Lovšin  Microbiology and immunology  Researcher  2015 - 2016  124 
4.  12189  PhD Janja Marc  Metabolic and hormonal disorders  Researcher  2013 - 2016  711 
5.  34223  PhD Tijana Markovič  Pharmacy  Researcher  2014  58 
6.  25809  PhD Vid Mlakar  Metabolic and hormonal disorders  Researcher  2013 - 2015  96 
7.  18154  PhD Barbara Ostanek  Metabolic and hormonal disorders  Researcher  2015 - 2016  187 
8.  01989  PhD Janez Preželj  Metabolic and hormonal disorders  Head  2013 - 2016  303 
9.  22657  PhD Irena Prodan Žitnik  Pharmacy  Researcher  2013 - 2016  48 
10.  32807  PhD Peter Vrtačnik  Pharmacy  Junior researcher  2013 - 2014  18 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  76,288 
2.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,522 
3.  1187  General hospital Celje  Celje  5064716  2,856 
Abstract
Osteoporosis is a common skeletal disease, characterized by low bone mass and microarchitectual deterioration of bone tissue, leading to increased risk of fracture. After the age of 50, osteoporosis affects every third woman and every fifth man. Osteoporosis is a multifactorial disease, influenced by genetic and environmental factors. Twin studies have shown that 50-85% variability in bone mineral density (BMD) is influenced by genetic component. However, despite the effort involved in the identification of novel osteoporosis-related genes, only a small part of the genetic background of the disease have been explained. On the basis of these results, it is suggested that other unidentified processes, involved in gene expression regulation, could be of great importance. Recent studies have shown that the regulation of gene expression is markedly influenced by micro RNA (miRNA). miRNA is a short RNA molecule, involved in the degradation of mRNA. It has been shown that miRNAs have an important role in the pathogenesis of different diseases, such as myocardial infarction, stroke and malignant diseases. Additionally, animal studies and experiments in cell lines have clearly shown that miRNAs also regulate differentiation and function of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) and, therefore, influence bone metabolism. So far, there has been only a few studies published, linking miRNAs with osteoporosis. Although research of miRNA is a very perspective field with excellent opportunity for use in clinical practice, a key problem for the diagnostic use remains unsolved - a lack of knowledge of bone specific miRNA expression. The main aim of proposed project will be the identification of miRNAs that are involved in the regulation of bone metabolism and could, therefore, be used as good biomarkers for the diagnosis of osteoporosis and targets for its treatment. Because of their stability in plasma, these miRNA could be used as potential targets for development of non-invasive in vitro diagnostic tests for osteoporosis. Finally, these miRNA could also be a target for new active substances – antagomers. To obtain the main goal of the project, we will first identify miRNA that are present in human plasma. To identify bone-specific miRNA in human plasma, it will be necessary to explore miRNA profiles of human osteoblasts in different physiological-like conditions. Osteoblasts will be studied due to their central role in bone biology, acting as bone forming cells as well as the regulatory cells of osteoclasts activity through RANK/RANKL/OPG regulatory pathway. Osteoblast-specific miRNA in human plasma will be obtained by comparison of miRNA profiles of human plasma and human osteoblasts. Osteoblast-specific miRNA in human plasma will be subjected to in vitro functional analysis to explore the role of the identified miRNAs in osteoblast-specific mRNA regulation and involvement in bone metabolism. Additionally, functionally relevant osteoblast-specific miRNA, detectable also in human plasma, will be clinically evaluated in patients with and without osteoporosis. So far, such approach has not been used in osteoporosis and will significantly improve our understanding of the role of epigenetic mechanisms in osteoporosis that are expected to contribute to the genetic influence on the development of osteoporosis. Moreover, the use of plasma miRNA measurement for diagnosis of osteoporosis presents a completely new and original goal. In addition, the identified osteoblast-specific miRNAs could also present targets for the development of antagomers – anti-miRNA substances that bind to specific miRNAs. Binding of antagomer to miRNA prevents binding of miRNA to its target mRNA leading to changes in mRNA stability.
Significance for science
The increased incidence of osteoporosis and osteoporotic fractures caused by aging of the world population represents a serious problem. Due to huge economic burden and decreased quality of life, a lot of research is going on to discover the molecular mechanisms of its pathogenesis in order to obtain novel targets for the treatment or prevention of osteoporosis, early diagnostic markers for identification of individuals at higher risk for the development of osteoporosis and prognostic markers for an effective individualized therapy. Early diagnosis is especially important since most treatment strategies prevent further bone loss, instead of enhancing bone formation. Results of this project represent an important contribution to the understanding of the role of epigenetic mechanisms in osteoporosis and are of paramount importance for the patients and the whole society. They have the potential to contribute to the development of new diagnostic biomarkers and treatments and thus to improvement in osteoporosis care in the future.
Significance for the country
• New knowledge about demanding miRNA analysis, gained during the project, represents the basis for the development of new diagnostic test in the field of osteoporosis or also some other disease and thus introduction of a new test on the market. • New knowledge and collected samples and data foster collaboration with foreign research groups, thus increasing the probability to obtain new European and other funds for financing our future research work. • Early identification and treatment of subjects at risk can help prevent the consequences of osteoporosis, therefore our results have important implications for the protection of health especially in the elderly, the number of which is increasing also in Slovenia. This contributes to better quality of life and lower healthcare costs. • Contribution to the recognition of University of Ljubljana, other collaborating institutions and Slovenian scientists and therefore also recognition and reputation of Slovenia by already realized and planned publications and invited lectures on congresses. • Important contribution of the project to all levels of university education. Namely, members of the project team implement novelties from their research work in undergraduate and especially postgraduate studies, thus contributing to the development of high quality professionals and improvement of learning process.
Most important scientific results Annual report 2013, 2014, 2015, final report
Most important socioeconomically and culturally relevant results Annual report 2013, 2014, 2015, final report
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