Biomarkers of Joint Damage in Osteoarthritis: Current Status and Future Directions

Abstract

Osteoarthritis (OA) is a disease of the whole joint organ, characterized by the loss of cartilage, and structural changes in bone including the formation of osteophytes, causing disability and loss of function. It is also associated with systemic mediators and low-grade inflammation. Currently, there is negligible/no availability of specific biomarkers that can be used to facilitate the diagnosis and treatment of OA. The most unmet clinical need is, however, related to the monitoring of disease progression over a short period that can be used in clinical trials. In this review, the value of biomarkers identified over the past decade has been highlighted. These biomarkers are associated with the synthesis and breakdown of cartilage, including collagenous and noncollagenous biomarkers, inflammatory and anti-inflammatory biomarkers, expressed in the biological fluid such as serum, synovial fluid, and urine. Broad validation of novel and clinically applicable biomarkers and their involvement in the pathways are particularly needed for early-stage diagnosis, monitoring disease progression, and severity and examining new drugs to mitigate the effects of this highly prevalent and debilitating condition.

Anti-Inflammatory and Analgesic Effects of Schisandra chinensis Leaf Extracts and Monosodium Iodoacetate-Induced Osteoarthritis in Rats and Acetic Acid-Induced Writhing in Mice

“…Furthermore, TNF-α blocks the chondrocyte synthesis of proteoglycans and type II collagen. IL-1β activates transcription factors via the MAPK and NF-κB signalling pathways to regulate inflammatory responses, resulting in the production of inflammatory mediators such as NO, PGE2, COX-2, and other catabolic factors that may accelerate cartilage degeneration [ 30 , 31 , 32 ]. Moreover, cytokines upregulate the gene expression of MMPs, which promotes the degradation of articular cartilage by breaking down proteoglycan, the main component of the ECM [ 33 , 34 ].…”

Adherence to the OARSI recommendations for designing, conducting, and reporting of clinical trials in knee osteoarthritis: a targeted literature review

“…A deficiency across clinical trials that was found in the current review was a lack of reporting on biochemical biomarkers. Specific biomarkers related to metabolic changes due to KOA may be used for monitoring its progression, as well as for treatment development [ 35 , 36 ]. This is a topic that is gaining interest in KOA research, especially since current trials focus mostly on PROs and are unable to show metabolic changes of therapies on joint tissues.…”

“…This is a topic that is gaining interest in KOA research, especially since current trials focus mostly on PROs and are unable to show metabolic changes of therapies on joint tissues. However, there is currently no consensus on the collection of a specific set of biomarkers, as only a small number of biomarkers involved in the development of KOA have been identified so far [ 10 , 36 – 38 ]. For example, Yang et al (2015) showed that treatment with HA injections significantly reduced the concentration of cytokine interleukin-1β (IL-1β) in synovial fluid [ 39 ], while a study by Henrotin et al (2017) reported decreased levels of serum Coll2–1 [ 40 ].…”

Current and novel theranostic modalities for knee osteoarthritis

“…Cartilage oligomeric matrix protein is a component of cartilage tissue and synovial fluid. Since this protein is present only in this organ, its measurement in the blood can indicate the destruction or repair of the cartilage tissue [43]. HA as another marker, is one of the heavy molecules of glucosamine, which is a component of connective tissue.…”