Evaluation of serum mirna MİR-26A, MİR-29A, MİR-133A) expression levels in patients with osteogenesis imperfecta

Evaluation of Serum miRNA (mir-26a, mir-29a, mir-133a) Expression Levels in Patients with Osteogenesis Imperfecta Objective: Osteogenesis Imperfecta (OI) is associated with long bone deformities and fractures, accompanied by a genetic connective tissue disorder with visible blue sclera, tooth disturbances, hearing loss and ligamentous laceration. According to their clinical, inherited, and radiological characteristics, OI is classically divided into four classes by Sillence et al. So far 17 different types of OI has been reported in OMIM (Online Mendelian Inheritance in Man) database. There are autosomal dominant (OD) and autosomal recessive (OR) transitions, although inheritance patterns differ according to types. Until recently, our classical knowledge has been described as central dogma, in which DNA stored in genetic material is transcribed into messenger RNA (mRNA) and then carried by transporter RNA (tRNA) to move to ribosomes to synthesize the necessary proteins. However, genome and functional analysis studies have shown the presence of non-coding RNA (ncRNA) molecules. MicroRNAs (miRNAs), a class of small non-coding RNAs, play important roles in processes such as development, homeostasis, immune system and ossification. miRNAs have been shown to be associated with a variety of diseases from inflammation to cancer. Existing evidence suggests that miRNAs affect the expression of target mRNAs by binding and suppression in the process of ossification which in turn influence the osteoblastic proliferation, differentiation and osteoclastic activating translational products. miR-26a, miR-29a, miR-133a are believed to be associated with bone tissue. In this study we aimed to identify the role of microRNAs in the clinical heterogenity of OI, contribute to the understanding of their utility as biomarker, and also to determine the expression differences of bone-associated miRNAs (miR-26a, miR29a, miR-133a) between the patients and healthy controls in order to search for their possibile use as a new therapeutic target. Method: Control group was made up of healthy children between the ages of 0 and 18 who applied to the General Child Policlinic of Akdeniz University Medical School. Patient group was 0-18 age children, followed by OI diagnosis in Akdeniz University Medical School, Endocrinology and Child Genetics Departments. MiRNeasy Serum / Plasma Kit (Qiagen, 217184) was used for the isolation of miRNA (mir-26a, mir-29a, mir-133a) from the plasma samples of the participants. The values determined by quantitative PCR were normalized using the REST programme (Pfaffl MW et al., Nuc Acid Res, 2002; 30 (9): E36). Results: There was a noticeable difference between the miRNA levels of the patient and control groups and the miRNA levels of the patient group were higher. Serum calcium and vitamin D levels of patients with higher mir133a levels were lower than those of the other groups. There was no statistically significant difference between the incidence of dentinogenesis imperfecta and miRNA levels. However, expression of miR26a was significantly increased in dentinogenesis imperfectant patients (p = 0.09). Conclusion: OI is characterized by diffuse osteoporosis, recurrent bone fractures and resulting deformities, and there is no definitive treatment. Identification of biomarkers may be important in the diagnosis and follow-upof OI, detection of the disease at an early stage, monitoring the response to treatment, and determining miRNAs that are likely to be a new therapeutic targets. microRNAs are shedding light on early detection and possible treatments by shedding light on the dark areas of some diseases. Osteogenesis Imperfecta is also one of these diseases. Although there is need for more sufficient and extensive clinical trials currently microRNAs can be used as biomarkers Key Words: Osteogenesis Imperfecta, microRNA, miR-26a, miR-29a, miR-133a