ICRS 2019 - Conference Calendar
7.0.1 - Molecular Targets
7.0.2 - Biomarkers
A biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” 1. Biomarkers may be biochemicals, images, visual analog scales (VAS) or combinations of these. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Biomarkers are also known as biochemical markers, molecular markers or signature molecules. The terms “biomarker”, “soluble biomarker”, “molecular biomarker” and “biochemical marker” are frequently used to describe soluble biological molecules that may be used as a sign of a normal or abnormal process, or of a condition or disease. Biomarkers may be found in cells, tissues the extracellular matrix (ECM) or in the secretions of cells (i.e. the so-called “secretome”). Clinically they may be detected and measured in body fluids such as blood, serum, plasma and urine. In the fields of rheumatology and orthopaedics biomarkers provide useful diagnostic and prognostic information by detecting joint tissue degradation in diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA).
). In OA biomarkers have the capacity to reflect disease-relevant biological activity and predict the course of disease progression 2. Although all joint tissues are implicated in disease progression in OA, articular cartilage has received the most attention in the context of aging, injury and disease . There is increasing emphasis on the early detection of OA as it has the capacity to target and treat the disease more effectively 3. In this era of personalized and precision medicine soluble biomarkers can be powerful tools for the diagnosis, prognosis and personalized management of OA 4. However, the development of personalized strategies for the prevention and treatment of OA require new and sensitive biomarker tools that can detect the disease in its molecular and pre-radiographic stage, before structural and functional alterations in cartilage integrity have occurred. At the present time, the available biomarkers in our toolbox do not have the capacity to detect and define early OA or understand the emerging endotypes and phenotypes of this disease 5. Furthermore, most of the research in the field of OA biomarkers has focused on the development of biomarker assays for cartilage matrix degradation mediated by catabolic and pro-inflammatory mediators. Significantly less attention has been paid to the development of biomarker tools and assays that reflect cartilage repair and regeneration in the context of anabolic stimulation. The field of cartilage repair, regeneration and joint preservation will benefit from the identification and validation of biomarkers that can help understand the mode of action of growth factors, stem cells and biomaterials. Many newly synthesised ECM molecules can serve as biomarkers of new cartilage formation but there are only a handful of biomarker assays available for the quantitative assessment of new cartilage formation. This presentation will focus on cell and matrix-derived biomarkers of cartilage repair and regeneration, cytoprotective factors and neo-epitopes of new cartilage matrix formation. Further research using conventional techniques, advanced analytical platforms and “omics” technologies such as proteomics will shed further light on this important topic and promote collaboration between investigators in the fields of cartilage degradation in OA and cartilage repair and joint preservation.
Keywords: Biomarker; osteoarthritis (OA); extracellular matrix (ECM); cytoprotective factors; proteomics; cartilage degradation; cartilage repair; joint preservation
1. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001 Mar;69(3):89–95.
2. Mobasheri A. Osteoarthritis year 2012 in review: biomarkers. Osteoarthr Cartil. 2012 Dec;20(12):1451–1464.
3. Mobasheri A, Henrotin Y. Biomarkers of (osteo)arthritis. Biomarkers. 2015;20(8):513–518.
4. Henrotin Y, Sanchez C, Bay-Jensen AC, Mobasheri A. Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives. Ann Phys Rehabil Med. 2016 Jun;59(3):145–148.
5. Van Spil WE, Kubassova O, Boesen M, Bay-Jensen A-C, Mobasheri A. Osteoarthritis phenotypes and novel therapeutic targets. Biochem Pharmacol. 2019 Jul;165:41–48.