Soluble biological markers in osteoarthritis

Abstract

In recent years, markers research has focused on the structural components of cartilage matrix. Specifically, a second generation of degradation markers has been developed against type II collagen neoepitopes generated by specific enzymes. A particular effort has been made to measure the degradation of minor collagens III and X of the cartilage matrix. However, because clinical data, including longitudinal controlled studies, are very scarce, it remains unclear whether they will be useful as an alternative to or in combination with current more established collagen biological markers to assess patients with osteoarthritis (OA). In addition, new approaches using high-throughput technologies allowed to detect new types of markers and improve the knowledge about the metabolic changes linked to OA. The relative advances coming from phenotype research are a first attempt to classify the heterogeneity of OA, and several markers could improve the phenotype characterization. These phenotypes could improve the selection of patients in clinical trials limiting the size of the studies by selecting patients with OA characteristics corresponding to the metabolic pathway targeted by the molecules evaluated. In addition, the inclusion of rapid progressors only in clinical trials would facilitate the demonstration of efficacy of the investigative drug to reduce joint degradation. The combination of selective biochemical markers appears as a promising and cost-effective approach to fulfill this unmet clinical need. Among the various potential roles of biomarkers in OA, their ability to monitor drug efficacy is probably one of the most important, in association with clinical and imaging parameters. Biochemical markers have the unique property to detect changes in joint tissue metabolism within a few weeks.

Identification of plasma and urinary inflammatory markers in severe knee osteoarthritis: Relations with synovial fluid markers

“…In the field of biomarker research, cartilage markers have been the subject of comprehensive and in-depth studies. In line with the findings of previous studies [ 12 , 37 ], our study reaffirmed the elevation of promising OA biomarkers, namely, pHA and uCTX-II, in severe knee OA. Additionally, we observed increased urinary levels of COMP, HA, MMP-1, and MMP-3 in severe knee OA patients compared with controls.…”

“…Joint synovial fluid (SF) contains substances related to OA pathophysiology, including inflammatory mediators, cartilage-degrading enzymes, and cartilage-derived products; thus, it occupies an important position in biomarker research for OA. However, limitations in developing and clinically applying SF-based biomarkers exist due to the invasiveness of sample collection, variations in the presence of SF, and the skilled techniques required for collection [ 12 ]. Recently, blood or urine, which can be collected by a less invasive route, have been applied in biomarker research as a surrogate matrix for SF.…”

Transcriptomic analyses and machine-learning methods reveal dysregulated key genes and potential pathogenesis in human osteoarthritic cartilage

“…This implies that studies based on the expression and translation levels of these four hub genes in synovial fluid, blood, and urine possess clinical importance, and that changes in these candidate biomarkers may play a vital role in the detection of OA. 41 To further explore the potential molecular mechanisms of the four key genes in OA, we constructed a PPI network based on these crucial genes through the GeneMANIA database. Annotation of the gene functions through KEGG and GO analyses revealed that the neurotrophin signalling pathway, the thyroid hormone signalling pathway, the PI3K-Akt signalling pathway, thyroid hormone generation, the positive regulation of apoptotic signalling pathway, and the stress-activated mitogen-activated protein kinase (MAPK) cascade were the most important functional categories.…”

Emerging molecular biomarkers in osteoarthritis pathology

“…Despite this, inflammation is still an important contributor to the development and progression of OA, even in the early stages. 18 Structural alterations in the OA-inflicted joint are hypothesized to be linked, at least in part, to multiple proinflammatory cytokines. 57 The role of inflammatory mediators in human OA has been extensively reviewed.…”

“…As OA appears to diagnose and prognose joint disease progression over weeks or months, as opposed to years. In this regard, recent studies suggest the association of biomarkers, such as noncoding RNAs, 12 metabolites, 13 inflammatory markers, [14][15][16] and cartilage degradation products 17,18 with OA pathology (Figure 1), as well as other biomarker entities (e.g. epigenetic and microbial) reviewed in detail elsewhere.…”