Biomarkers of Hand Osteoarthritis Are Detectable after Mechanical Exercise.

BACKGROUND: Hand osteoarthritis (OA) is one of the most common joint diseases, but studies on biomarkers are rare. The aim of this explorative study was (a) to evaluate potential biomarkers of hand OA, (b) to identify an optimal time point to sample venous blood, and (c) to correlate biomarker levels with radiological and clinical scores. METHODS: Four female cohorts were investigated. One with a more Heberden-accentuated OA and one with a more Bouchard-accentuated hand OA, and two symptom-free control groups aged 20-30 or 50-75 years. The venous blood was sampled before and at eight time points after mechanical exercise of the OA hand. X-rays of OA hands were assessed using the Kellgren and Lawrence as well as Kallman scores. Participants were evaluated clinically using the AUSCAN™ Index, visual analog scale (VAS), and Health Assessment Questionnaire (HAQ). Serum levels of seven biomarkers were measured by ELISA. RESULTS: The concentrations of CPII, COMP, IL-15, sVCAM-1, NGAL, and PIIANP were significantly increased within 15 min after exercise. PIIANP was markedly elevated in the Heberden-accentuated OA group as compared to both control groups, but did not correlate with any radiological or clinical score. Analysis of the probabilistic index further revealed that CPII can distinguish between Bouchard's OA and premenopausal controls whereas COMP can discriminate between Bouchard's and Heberden's OA. CONCLUSIONS: This study demonstrates that even previously undetectable biomarkers can be quantified in serum after mechanical exercise. Future larger studies are needed to determine specificity and sensitivity of these markers and their ability to diagnose even pre-radiological OA.

Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species.

BACKGROUND: Hyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA). METHODS: We used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis. RESULTS: Compared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs. CONCLUSIONS: The levels, composition, and MW distribution of all currently known lubricants in SF--HA, lubricin, PLs--vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction.

Sphingolipids in human synovial fluid--a lipidomic study.

Articular synovial fluid (SF) is a complex mixture of components that regulate nutrition, communication, shock absorption, and lubrication. Alterations in its composition can be pathogenic. This lipidomic investigation aims to quantify the composition of sphingolipids (sphingomyelins, ceramides, and hexosyl- and dihexosylceramides) and minor glycerophospholipid species, including (lyso)phosphatidic acid, (lyso)phosphatidylglycerol, and bis(monoacylglycero)phosphate species, in the SF of knee joints from unaffected controls and from patients with early (eOA) and late (lOA) stages of osteoarthritis (OA), and rheumatoid arthritis (RA). SF without cells and cellular debris from 9 postmortem donors (control), 18 RA, 17 eOA, and 13 lOA patients were extracted to measure lipid species using electrospray ionization tandem mass spectrometry--directly or coupled with hydrophilic interaction liquid chromatography. We provide a novel, detailed overview of sphingolipid and minor glycerophospholipid species in human SF. A total of 41, 48, and 50 lipid species were significantly increased in eOA, lOA, and RA SF, respectively when compared with normal SF. The level of 21 lipid species differed in eOA SF versus SF from lOA, an observation that can be used to develop biomarkers. Sphingolipids can alter synovial inflammation and the repair responses of damaged joints. Thus, our lipidomic study provides the foundation for studying the biosynthesis and function of lipid species in health and most prevalent joint diseases.

A lipidomic study of phospholipid classes and species in human synovial fluid.

OBJECTIVE: Membrane phospholipid species contribute to boundary lubrication that is provided by synovial fluid (SF). Altered levels of lubricants can be associated with increased friction, leading to articular cartilage damage. This study was undertaken to determine whether the composition of phospholipid species is altered in diseases of human knee joints. METHODS: The study was performed using SF from unaffected controls and patients with early osteoarthritis (OA), late OA, or rheumatoid arthritis (RA). Lipids were extracted from cell- and vesicle-free SF from 9 control donors postmortem and from 17 patients with early OA, 13 patients with late OA, and 18 patients with RA. Phospholipid species were quantified by electrospray ionization tandem mass spectrometry. RESULTS: We conducted lipidomic analysis to provide the first detailed overview of phospholipid species in human SF. We identified 130 lipid species belonging to 8 lipid classes (phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, plasmalogens, phosphatidylserine, phosphatidylglycerol, sphingomyelin, and ceramide). Compared to SF from controls, SF from patients with early OA and those with late OA had higher levels of most phospholipid species. Moreover, the concentrations of 64 and 27 phospholipids differed between RA and early OA SF and between RA and late OA SF, respectively. Also, the levels of 66 phospholipid species were altered in early OA versus late OA. CONCLUSION: Our data indicate disease- and stage-dependent differences in the relative composition and levels of phospholipid species in human SF. Such alterations might affect articular joint lubrication. Because certain phospholipids scavenge reactive oxygen species (ROS) and are pro- or antiinflammatory, any altered phospholipid level might influence ROS-scavenging activity of SF and the inflammatory status of joints. Thus, phospholipids may be associated with the pathogenesis of OA.