Objective. To investigate whether alarmins S100A8 and S100A9 are involved in mediating cartilage destruction during murine and human osteoarthritis (OA).Methods. Two different murine models of OA that differed in terms of synovial activation were compared. Cartilage destruction was measured histologically. Synovial biopsy and serum samples from OA patients were derived from the Cohort Hip and Cohort Knee (CHECK) patients with symptomatic early OA. Expression of mediators in the synovium was measured by reverse transcription-polymerase chain reaction analysis and immunolocalization.Results. In collagenase-induced OA, which showed marked synovial activation, interleukin-1␤ was expressed at significant levels only during the early stages of disease, whereas S100A8 and S100A9 expression remained high for a prolonged period of time (up to day 21 after induction). In S100A9-knockout mice, we found a major impact of S100A8 and S100A9 on synovial activation (62% inhibition) and OA cartilage destruction (45-73% inhibition) as compared to wild-type controls. In contrast, in the surgically induced destabilized medial meniscus model, in which synovial involvement is scant, we found no role of S100A8 and S100A9 in the focal OA cartilage destruction. Examination of arthroscopic synovial biopsy samples from patients in the early symptomatic OA CHECK cohort revealed substantial levels of S100A8 and S100A9 messenger RNA and protein, which correlated significantly with synovial lining thickness, cellularity in the subintima, and joint destruction. Levels of S100A8/A9 serum protein were significantly enhanced (19%) at baseline in patients who had pronounced progression of joint destruction after 2 years.Conclusion. Our data suggest that the S100A8 and S100A9 proteins are crucially involved in synovial activation and cartilage destruction during OA and that high levels may predict joint destruction in humans with OA.

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Objective To describe the osteoarthritis study population of CHECK (Cohort Hip and Cohort Knee) in comparison with relevant selections of the study population of the Osteoarthritis Initiative (OAI) based on clinical status and radiographic parameters. Methods In The Netherlands a prospective 10-year follow-up study was initiated by the Dutch Arthritis Association on participants with early osteoarthritis-related complaints of hip and/or knee: CHECK. In parallel in the USA an observational 4-year follow-up study, the OAI, was started by the National Institutes of Health, on patients with or at risk of symptomatic knee osteoarthritis. For comparison with CHECK, the entire cohort and a subgroup of individuals excluding those with exclusively hip pain were compared with relevant subpopulations of the OAI. Results At baseline, CHECK included 1002 participants with in general similar characteristics as described for the OAI. However, significantly fewer individuals in CHECK had radiographic knee osteoarthritis at baseline when compared with the OAI (p<0.001). In contrast, at baseline, the CHECK cohort reported higher scores on pain, stiffness and functional disability (Western Ontario and McMaster osteoarthritis index) when compared with the OAI (all p<0.001). These differences were supported by physical health status in contrast to mental health (Short Form 36/12) was at baseline significantly worse for the CHECK participants (p<0.001). Conclusion Although both cohorts focus on the early phase of osteoarthritis, they differ significantly with respect to structural (radiographic) and clinical (health status) characteristics, CHECK expectedly representing participants in an even earlier phase of disease.

Objective. The treatment of patients with fibromyalgia (FM), a high-prevalence chronic pain condition with a high impact on both patients and society, poses a great challenge to clinicians due to a lack of effective treatments. In view of the large individual variability in outcome, selecting patients at risk of long-term dysfunction and offering tailored treatment may be promising for beneficial treatment effects. Methods. High-risk patients were selected and classified into 2 groups (pain-persistence and pain-avoidance groups) and subsequently randomized in groups to either a treatment condition (TC) or a waiting list control condition (WLC). Treatment consisted of 16 sessions of cognitive-behavioral therapy (CBT) and exercise training in groups, tailored to the patient's specific cognitive-behavioral pattern, delivered within 10 weeks. Physical and psychological functioning and impact of FM were assessed at baseline, posttreatment, and 6-month followup. Treatment effects were evaluated using a linear mixed model. Results. The treatment effects were significant for all primary outcomes, showing significant differences in physical (pain, fatigue, and functional disability) and psychological (negative mood and anxiety) functioning, and impact of FM for the TC in comparison with the WLC. Effect sizes in the TC were overall large, and reliable change indices indicated a clinically relevant improvement among the TC. Conclusion. The presented results demonstrate for the first time that tailored CBT and exercise training for high-risk patients with FM is effective in improving short-and long-term physical and psychological functioning, indicating that tailoring treatment is likely to promote beneficial outcomes in FM and reduce the burden for patients and society.

The serum MMP-3 level seems to be an indicator for the development of radiological damage in patients with early RA and appears to be particularly indicative of cartilage degradation.