Classification of Osteoarthritis Biomarkers

FACULTY OF ENVIRONMENTAL MEDICINE

DEPARTMENT OF FOREIGN LANGUAGES

 

 

OSTEOARTHRITIS BIOMARKERS

 

Done:

Master course: Marina Markevich

__________________ 2017

 

 

Teacher of English: Natalja Gritsay _____________________ 2017

 

 

Minsk 2017

Contents

 

1 Introduction....................................................................................................... 3

2 Main Body ……………………………………………………………………….4-13

2.1 Classification of Osteoarthritis Biomarkers ……………………………………….4

2.2 Catabolic Osteoarthritis Biomarkers ………………………………………... 5

2.2.1C-Telopeptides of Type II Collagen...................................................... 5

2.2.2 Cartilage Oligomeric Matrix Protein.................................................... 5

2.2.3Hyaluronic Acid………………………………………………………...... 6

2.3 Post-Genomic Osteoarthritis Biomarkers..................................................... 7

2.3.1Transcriptomic Osteoarthritis Biomarkers............................................. 7

2.3.2 Proteomic Biomarkers............................................................................ 8

2.3.3 Metabolomic Biomarkers........................................................................ 9

2.4 MicroRNAs Biomarkers in Osteoarthritis.................................................11

2.4.1MicroRNA and Its Biogenesis..............................................................11

2.4.2MicroRNA Biomarkers in Joint Tissues.............................................11

2.4.3Promising Circulating MicroRNA Biomarkers.................................... 12

3 Conclusion....................................................................................................... 14

4 References........................................................................................................ 15

 

 

Introduction

Osteoarthritis (OA) is a long-lasting chronic inflammation of the joints with their degenerative-dystrophic changes.In recent years the relationship between the induction of inflammatory and degenerative diseases of the joints with the effect of negative environmental factors (hypothermia and the effect of chemical toxins) or joint trauma has been widely discussed. In addition, such factors as age, genetic predisposition, gender, metabolic status and obesity contribute to the likelihood of developing the disease. Hence, the timely diagnosis and prognosis of the disease on the basis of the identified biomarkers of disease are of importance. Among the likely candidates associated with osteoarthritis are catabolic biomarkers (urinary C-terminal telopeptide of type II collagen and cartilage oligomeric matrix protein), post-genomic biomarkers and the MicroRNA [6].

Since type II collagen is the most abundant protein in cartilage, C-terminal telopeptide of type II collagen has become the widely accepted biomarker for assessing collagen breakdown. This component in cartilage degeneration may be released into blood, synovial fluid, and urine.It has been found that patients with high levels of C-terminal telopeptide of type II collagen had the increased risk of having osteoarthritis of the knee and hip joints, in comparison with the patients with its low level. Cartilage oligomeric matrix protein correlates with cartilage degradation and determines the severity level of the osteoarthritis.In addition to these biomarkers, hyaluronic acid is also included in the group of catabolic biomarkers. Hyaluronic acid serum level is used as a biomarker to predict osteoarthritis of the knee.

The group of post-genomic biomarkers includes transcriptomic biomarkers, proteomic biomarkers and metabolomic biomarkers. Transcriptomic analysis has been performed with the gene microarrays or RNA sequencing to quantify the abundance of all transcripts in a particular biological specimen. Proteomic biomarkers clarify the information about the structure of the protein, thereby providing insight into the pathogenesis of the disease and are a powerful new tool for the study of biomarkers. Using liquid chromatography, scientists measured protein compositions in the cartilage of healthy patients and patients with osteoarthritis. Metabolomics is defined as the predominance of small molecular metabolites, the levels of which are determined as the final response of biological systems to environmental, genetic and other factors under normal or disease conditions. The ratio of serum metabolites such as valine to histidine and xleucine to histidine correlates with the severity of osteoarthritis of the knee [8].

MicroRNAs play an essential role in various physiological processes (cell proliferation, metabolism and apoptosis). Deregulation of microRNAs is associated with pathological conditions. MicroRNA-140 was found that during chondrogenesis, microRNA-140 upregulates its activity, but it is suppressed in chondrocytes in osteoarthritis. In serum, 3 microRNAs have been identified which have predicted the risk of developing osteoarthritis of hip and knee joints [13].

Thus, the study of biomarkers can help to ensure quality of improvement of the diagnosis, prognosis and understanding the pathogenesis of osteoarthritis.

Main Body

Classification of Osteoarthritis Biomarkers

In 2006, the National Institutes of Health (NIH) funded OA Biomarkers Network proposed a classification scheme for OA biomarkers represented by the acronym burden of disease, investigative, prognosis, efficacy, and diagnosis (BIPED) to connote the five categories of markers: Burden of Disease, Investigative, Prognostic, Efficacy of Intervention and Diagnostic [3]. Through the recent Osteoarthritis Research Society International (OARSI)/US Food and Drug Administration (FDA) initiative, the BIPED classification system added a sixth category, Safety of Interventions, to become BIPEDS [7].

The same OA biomarkers working group proposed to divide biomarkers in two major groups: wet biomarkers and dry biomarkers. The soluble or wet biomarkers are measured in blood, serum, plasma, urine, or synovial fluid and represent a modulation of endogenous substances in these fluids, whereas dry biomarkers consist of visual analog scales, performed tasks, or imaging [8].

Based upon the BIPEDS classification, Bauer et al. and Kraus et al. proposed the following clinical use of biological markers in OA [3, 7].

1. Diagnostic markers, as indicated by Bauer et al., are defined by the ability to classify individuals as either diseased or non-diseased with good positive and negative likelihood ratios and area under the curve in the receiving operator curve [3].

2. Burden of disease markers assess the severity or extent of disease, typically at a single point in time, among individuals with OA [3].

3. Prognostic markers predict the future onset of OA among those without OA at baseline or the progression of OA among those with existing disease. These biomarkers may be used to determine risk in those without OA, clinical outcomes in individuals with OA, or the efficacy of potential new disease-modifying osteoarthritis drugs (DMOADs) [3].

4. Efficacy of intervention markers provide information about the efficacy of treatment among those with OA or those at high risk of developing OA. These biomarkers can be used in randomized controlled trials (RCTs) to evaluate short- and long-term changes associated with DMOADs [3].

5. Investigative markers, as stated by Bauer et al., are one on which there is insufficient information to allow inclusion into one of the existing categories [3].

6. Safety of intervention markers provide information about exposure to new potential drugs, radiation, and contrast agents.

These biomarkers are expected to be of increasing significance as new biomarkers are identified and studied [7].