Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers

Abstract

Osteoarthritis affects over 250 million individuals worldwide. Currently, there are no options for early diagnosis of osteoarthritis, demonstrating the need for biomarker discovery. To find biomarkers of osteoarthritis in human synovial fluid, we used high performance liquid-chromatography mass spectrometry for global metabolomic profiling. Metabolites were extracted from human osteoarthritic (n = 5), rheumatoid arthritic (n = 3), and healthy (n = 5) synovial fluid, and a total of 1233 metabolites were detected. Principal components analysis clearly distinguished the metabolomic profiles of diseased from healthy synovial fluid. Synovial fluid from rheumatoid arthritis patients contained expected metabolites consistent with the inflammatory nature of the disease. Similarly, unsupervised clustering analysis found that each disease state was associated with distinct metabolomic profiles and clusters of co-regulated metabolites. For osteoarthritis, co-regulated metabolites that were upregulated compared to healthy synovial fluid mapped to known disease processes including chondroitin sulfate degradation, arginine and proline metabolism, and nitric oxide metabolism. We utilized receiver operating characteristic analysis to determine the diagnostic value of each metabolite and identified 35 metabolites as potential biomarkers of osteoarthritis, with an area under the receiver operating characteristic curve >0.9. These metabolites included phosphatidylcholine, lysophosphatidylcholine, ceramides, myristate derivatives, and carnitine derivatives. This pilot study provides strong justification for a larger cohort-based study of human osteoarthritic synovial fluid using global metabolomics. The significance of these data is the demonstration that metabolomic profiling of synovial fluid can identify relevant biomarkers of joint disease.

A biolabel research based on metabonomics reveals the therapeutic potentials of Herba Lysimachiae in synovial diseases

“…According to the pathway analysis of MetaboAnalyst, HL mainly affected two key pathways, that is, arachidonic acid metabolism and glycerophospholipid metabolism. Previous studies have shown that both pathways are closely associated with some synovial diseases, such as osteoarthritis and rheumatoid arthritis, which are involved in the pathogenesis of both diseases [13][14][15][16][17]. Previous proteomics study shows that HL also affects 4 key protein pathways (ribosome, RNA transport, hematopoietic cell lineage, and mRNA surveillance pathway), which may participate in the degenerative synovial diseases [2].…”

A discovery of screening markers for rheumatoid arthritis by liquid chromatography mass spectrometry: A metabolomic approach

“…[30][31][32] Other studies have shown a deficiency of both steroids, as well as other kinds of steroids, suggesting that RA is associated with the steroid pathway. 32,33 These steroids are known to be present in lower concentrations in patients who did not receive corticosteroid treatment compared to those who received treatment. 32 We confirmed that the patient group recruited for our study did not receive corticosteroid treatment.…”

Value of Biomarkers in Osteoarthritis

“…Proteomic studies, which reveal the protein content of the cell tissue and biological fluids, distinguish related proteins and show functional changes in proteins have become more prominent in recent years [55]. In 2011, studies describing new proteomes in the urine, serum, and chondrocyte vesicles of OA patients were published [56].…”