Osteoarthritis year 2011 in review: biochemical markers of osteoarthritis: an overview of research and initiatives

SummaryThe “year in review” session is a key moment of the Osteoarthritis Research Society International (OARSI) Congress. This is a unique opportunity for opinion leaders to summarize and comment the recent advances in one particular field of osteoarthritis research. This review is a summary of selected studies related to soluble biomarkers published between September 1st, 2010 and August 30th, 2011 and identified by a pubmed search using the terms “biomarkers” and “osteoarthritis”. In addition, I have selected some works presented during the 2011 OARSI Congress. This year was dominated by the publication of a consensus paper on the qualification of osteoarthritis (OA) biomarkers by the OARSI/Food Drug Administration (FDA) Osteoarthritis Biomarkers Working Group, and of proteomes of chondrocyte vesicles, urine and serum

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis - An open clinical trial-

BACKGROUND: Pentosan polysulfate sodium (pentosan) is a semi-synthetic drug manufactured from beech-wood hemicellulose by sulfate esterification of the xylopyranose hydroxyl groups. From in vitro and animal model studies, pentosan has been proposed as a disease modifying osteoarthritis drug (DMOAD). The objective of this study was to assess the efficacy, safety, and patient satisfaction in patients with mild radiographic knee osteoarthritis (OA) findings and OA-associated symptoms and signs. METHODS: Twenty patients were assessed clinically at Nagasaki University Hospital. The radiographic indications of OA were grade 1 to 3 using the Kellgren-Lawrence Grading System (K/L grade). Pentosan used in this study was manufactured and supplied in sterile injectable vials (100 mg/ml) by bene GmbH, Munich, Germany. The study was a single-center, open-label trial. Treatment consisted of 6 weekly subcutaneous injections (sc) of pentosan (2 mg/kg). Patients were clinically assessed at entry and 1 to 8, 11, 15, 24 & 52 weeks post treatment. The results were analyzed using one way ANOVA and Dunnett's method. RESULTS: Hydrarthroses were reduced quickly in all cases. The clinical assessments, i.e., knee flexion, pain while walking, pain after climbing up and down stairs, etc, were improved significantly and these clinical improvements continued for almost one year. The dose used in this study affected the blood coagulation test, but was within safe levels. Slightly abnormal findings were noted in serum triglycerides. CONCLUSIONS: Pentosan treatment in twenty patients with mild knee OA seemed to provide improvements in clinical assessments and C2C level of cartilage metabolism

Physiological effects of oral glucosamine on joint health: Current status and consensus on future research priorities

The aim of this paper was to provide an overview of the current knowledge and understanding of the potential beneficial physiological effects of glucosamine (GlcN) on joint health. The objective was to reach a consensus on four critical questions and to provide recommendations for future research priorities. To this end, nine scientists from Europe and the United States were selected according to their expertise in this particular field and were invited to participate in the Hohenheim conference held in Aug

Isothiocyanates are detected in human synovial fluid following broccoli consumption and can affect the tissues of the knee joint

Osteoarthritis is a major cause of disability and there is no current pharmaceutical treatment which can prevent the disease or slow its progression. Dietary advice or supplementation is clearly an attractive option since it has low toxicity and ease of implementation on a population level. We have previously demonstrated that sulforaphane, a dietary isothiocyanate derived from its glucosinolate precursor which is found in broccoli, can prevent cartilage destruction in cells, in in vitro and in vivo models of osteoarthritis. As the next phase of this research, we enrolled 40 patients with knee osteoarthritis undergoing total knee replacement into a proof-of-principle trial. Patients were randomised to either a low or high glucosinolate diet for 14 days prior to surgery. We detected ITCs in the synovial fluid of the high glucosinolate group, but not the low glucosinolate group. This was mirrored by an increase in ITCs and specifically sulforaphane in the plasma. Proteomic analysis of synovial fluid showed significantly distinct profiles between groups with 125 differentially expressed proteins. The functional consequence of this diet will now be tested in a clinical trial

Association of urinary biomarker COLL2-1NO-2 with incident clinical and radiographic knee OA in overweight and obese women

__Objective:__ To investigate the association between urinary biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA). __Design:__ Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index≥27kg/m2 without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses. __Results:__ 254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55-0.99). The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome. Conclusions: In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO2 concentration was significantly associa

Evaluation of differentiated bone cells proliferation by blue shark skin collagen via biochemical for bone tissue engineering

Collagen from a marine resource is believed to have more potential activity in bone tissue engineering and their bioactivity depends on biochemical and structural properties. Considering the above concept, pepsin soluble collagen (PSC) and acid soluble collagen (ASC) from blue shark (Prionace glauca) skin were extracted and its biochemical and osteogenic properties were investigated. The hydroxyproline content was higher in PSC than ASC and the purified collagens contained three distinct bands α1, α2, and β dimer. The purity of collagen was confirmed by the RP-HPLC profile and the thermogravimetric data showed a two-step thermal degradation pattern. ASC had a sharp decline in viscosity at 20–30 °C. Scanning electron microscope (SEM) images revealed the fibrillar network structure of collagens. Proliferation rates of the differentiated mouse bone marrow-mesenchymal stem (dMBMS) and differentiated osteoblastic (dMC3T3E1) cells were increased in collagen treated groups rather than the controls and the effect was dose-dependent, which was further supported by higher osteogenic protein and mRNA expression in collagen treated bone cells. Among two collagens, PSC had significantly increased dMBMS cell proliferation and this was materialized through increasing RUNX2 and collagen-I expression in bone cells. Accordingly, the collagens from blue shark skin with excellent biochemical and osteogenic properties could be a suitable biomaterial for therapeutic application

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanisms by which articular cartilage maintains its integrity throughout our lifetime is not fully understood, however there are numerous regulatory pathways known to govern ECM turnover in response to mechanical stimuli. To further our understanding of this field, we envision that proteomic analysis of the secretome will provide information on how the chondrocyte remodels the surrounding ECM in response to load, in addition to providing information on the metabolic state of the cell. In this review, we attempt to summarize the recent mass spectrometry-based proteomic discoveries in healthy and diseased cartilage and chondrocytes, to facilitate the discovery of novel biomarkers linked to degenerative pathologies, such as osteoarthritis (OA)