Exercise on microRNA in Osteoarthritis
Condition: Osteoarthritis, Knee; Epigenetic Disorder; Quality of Life; Depression; Pain
MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Depression
Study type: Interventional

Summary: 
      The present study is a prospective cohort study. This study will be conducted to determine
      the change in miRNA levels with exercise in knee Osteoarthritis (OA) patients. The main
      questions that the study aims to answer are:

      Question 1: Does exercise therapy affect microrna expressions in patients with knee
      osteoarthritis?

      Question 2: Does exercise therapy affect quality of life, pain, functional status and
      depression level in patients with knee osteoarthritis?

      Participants; demographic information such as age, height, weight will be questioned.
      Exercises will performed twice a week under supervision and once a week as home program for
      eight weeks. Before and after exercise treatment, peripheral venous blood samples will taken
      from both groups. miRNA-146a, miRNA-155, miRNA-221-3p and miRNA-145 gene expressions will
      studied with the real-time PCR (polymerase chain reaction) method. miRNA-146a, miRNA-155, and
      miRNA-221-3p, miRNA-145 gene expressions will studied with the Real-time PCR method. The pain
      will evaluated with the Numeric Rating Scale (NRS), functional status with Western Ontario
      and McMaster Universities Osteoarthritis Index (WOMAC), depression level with the Beck
      Depression Inventory (BDI), and quality of life with Short Form-36 (SF-36).
    

Detailed description: 
      Osteoarthritis is a degenerative disease causing joint pain, stiffness, and limitation of
      motion with loss of cartilage, osteophyte development, subchondral sclerosis, changes in the
      joint capsule and synovial membrane as a result of the disruption of genetic, biomechanical,
      and biochemical balances. Pharmacological treatments of osteoarthritis include simple
      analgesics, non-steroidal anti-inflammatory drugs, opioids and topical analgesics. Patient
      education, self-management programs, exercise, weight loss, assistive devices and lifestyle
      changes are non-pharmacological treatment methods.Exercise is one of the basic elements of
      the treatment modality. The purpose of the exercise; to relieve symptoms and improve muscle
      strength around joints. It is aimed to increase the quality of life with the adaptation of
      individuals to exercise.

      miRNA, one of the small non-coding RNA subunits, is responsible for the modulation of
      protein-coding genes as a result of post-transcriptional repression. miRNA play an active
      role in many biological events such as cellular differentiation, apoptosis, proliferation,
      erythropoiesis, fibrosis and angiogenesis. Due to the role of miRNAs in normal development
      and diseases, it is thought that they will be a new biomarker for therapeutic purposes in the
      future. It was found that miRNAs play a key role in physiological conditions e.g. skeletal
      muscle hypertrophy, mitochondrial biogenesis, vascular angiogenesis, and metabolic events
      when combined with exercise. The identification of miRNAs that change in circulation with
      exercise is important in terms of providing new data on the physiological adaptation of
      exercise. In recent years, a large number of miRNAs have been identified in osteoarthritic
      tissues, which is important in terms of the regulation of gene expressions related to the
      pathogenesis of OA. OA-specific miRNA expressions is necessary for early diagnosis and
      treatment of OA as well as for monitoring the progression of the disease. It has been
      reported that miRNA-146a is intensely expressed in OA tissue and its expression is induced by
      inflammatory cytokines. MiRNA-145 is associated with chondrocyte homeostasis and is thought
      to be involved in the degradation of the extracellular matrix. MiRNA-155 is a miRNA that has
      a role in the development and regulation of innate and acquired immunity, and its expression
      is increased in tissues with OA compared to healthy tissue. It has an important role in
      hematopoiesis. MiRNA-221-3p was found to be associated with chondrocyte proliferation, gene
      expression, matrix degradation and apoptosis.

      In this study it was aimed to determine the changes in miRNA levels of knee OA patients with
      exercise.
    

Intervention name(s): Exercise Programme; Experiments
Intervention type(s): Other; Other
Intervention description(s): All patients were informed about knee OA, joint protection principles, and the exercise effects on knee OA before treatment. The exercises were supervised by a physiotherapist for 30 minutes twice a week and once a week as a home program. The exercise program consisted of a warm-up, strengthening knee extensors and lower extremity stretching exercises. Firstly, quadriceps isometric and adductor isometric (roll tightening) exercises, hamstring stretching, quadriceps stretching, and gastrocnemius stretching were applied. Then, hip flexion-extension-abduction-adduction, and knee extension while sitting were applied with exercise bands. Strengthening exercises were composed of three sets with 10 repetitions. Stretching exercises were performed 10 repetitions for 10 seconds.; The total RNA was isolated from peripheral blood samples taken from patients and the control group by applying the protocol of the manufacturer (LucigenMasterPure™ Complete DNA and RNA Purification Kit, USA). The total RNA was isolated in three steps: Lysis stage of the whole blood samples, precipitation of nucleic acids and precipitation of total RNA. The purity and concentration of the isolated total RNA samples were measured with the spectrophotometer (Thermo Fischer) device. The samples were stored at -80°C until the next step. To determine the microRNA expression levels; firstly, conjugate DNA (cDNA) was synthesized from total RNA samples according to the manufacturer's protocol. Whether the desired region reproduced in the reaction and whether there were primer dimers were checked by adding a melting curve step. In addition, blood samples of 30 age-sex matched healthy volunteers were compared.
Intervention model: Single Group Assignment
Intervention model description: Prospective Cohort Study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Osteoarthritis; Epigenetic Disorder; Quality of Life; Depression; Pain