Chemokines modulate chondrocyte homeostasis: implications in osteoarthritis

Non-alcoholic steatohepatitis (NASH) is an underdiagnosed liver disease characterized by steatosis, necroinflammation and fibrosis. This disease may eventually develop into cirrhosis and hepatocellular carcinoma. NASH is highly prevalent among obese individuals and among patients with diabetes mellitus type 2. Non-alcoholic fatty liver (NAFL), a precursor of NASH, is the main cause of elevated serum liver enzymes among the general population. In NASH the liver is programmed to lipogenesis rather than to glycogenesis and herein insulin-resistance plays a major role. Gradual weight loss, physical exercise and drugs that improve insulin sensitivity are potential therapie

The chemokine receptor CCR5 plays a role in post-traumatic cartilage loss in mice, but does not affect synovium and bone

SummaryObjectiveC–C chemokine receptor type 5 (CCR5) has been implicated in rheumatoid arthritis and several inflammatory diseases, where its blockade resulted in reduced joint destruction. However, its role in modulating cartilage and bone changes in post-traumatic osteoarthritis (OA) has not yet been investigated. In this study, we investigated changes in articular cartilage, synovium and bone in a post-traumatic OA model using CCR5-deficient (CCR5−/−) mice.MethodDestabilization of the medial meniscus (DMM) was performed on the right knee of 10-week old CCR5−/− and C57BL/6J wild-type (WT) mice to induce post-traumatic OA. The contralateral left knee served as sham-operated control. Knee joints were analyzed at 4-, 8- and 12-weeks after surgery to evaluate cartilage degeneration and synovitis by histology, and bone changes via micro-CT.ResultsOur findings showed that CCR5−/− mice exhibited significantly less cartilage degeneration than WT mice at 8- and 12-weeks post-surgery. CCR5−/− mice showed some altered bone parameters 18- and 22-weeks of age, but body size and weight were not affected. The effect of CCR5-ablation was insignificant at all time points post-surgery for synovitis and for bone parameters such as bone volume/total volume, connectivity density index (CDI), structure model index (SMI), subchondral bone plate thickness, and trabecular bone number, thickness and spacing.ConclusionThese findings suggest that CCR5−/− mice developed less cartilage degeneration, which may indicate a potential protective role of CCR5-ablation in cartilage homeostasis. There were no differences in bone or synovial response to surgery suggesting that CCR5 functions primarily in cartilage during the development of post-traumatic OA

Summary of the OA biomarkers workshop 2010 – genetics and genomics: new targets in OA

SummaryOn November fourth and fifth 2010 a group of more than 100 international investigators gathered in Atlanta for the second Osteoarthritis (OA) Biomarkers Global Initiative workshop titled “Genetics and Genomics: New Targets in OA”. The first workshop took place in April 2009 and focused on in vitro (soluble) biomarkers whilst the third and final workshop will take place in 2012 and will focus on imaging biomarkers. The OA Research Society International (OARSI) has organized the workshops. In addition to OARSI, the National Institute of Arthritis, Musculoskeletal and Skin Diseases, the Arthritis Foundation, Amgen, Genzyme, the American Orthopaedic Society for Sports Medicine and Pfizer sponsored the second meeting. It was clear from this meeting that experiments in the genetics, epigenetics and genomics of OA, are yielding valuable insights into the etiology of this heterogeneous disease but that much still needs to be learnt. Combining genetic insights with conventional biomarkers and imaging modalities may provide scientists with the enhanced tools to understand this complex disease. With those tools in hand, clinicians and industry can develop protocols to ultimately improve patient care

Non-Invasive Mouse Models of Post-Traumatic Osteoarthritis

SummaryAnimal models of osteoarthritis (OA) are essential tools for investigating the development of the disease on a more rapid timeline than human OA. Mice are particularly useful due to the plethora of genetically modified or inbred mouse strains available. The majority of available mouse models of OA use a joint injury or other acute insult to initiate joint degeneration, representing post-traumatic osteoarthritis (PTOA). However, no consensus exists on which injury methods are most translatable to human OA. Currently, surgical injury methods are most commonly used for studies of OA in mice; however, these methods may have confounding effects due to the surgical/invasive injury procedure itself, rather than the targeted joint injury. Non-invasive injury methods avoid this complication by mechanically inducing a joint injury externally, without breaking the skin or disrupting the joint. In this regard, non-invasive injury models may be crucial for investigating early adaptive processes initiated at the time of injury, and may be more representative of human OA in which injury is induced mechanically. A small number of non-invasive mouse models of PTOA have been described within the last few years, including intra-articular fracture of tibial subchondral bone, cyclic tibial compression loading of articular cartilage, and anterior cruciate ligament (ACL) rupture via tibial compression overload. This review describes the methods used to induce joint injury in each of these non-invasive models, and presents the findings of studies utilizing these models. Altogether, these non-invasive mouse models represent a unique and important spectrum of animal models for studying different aspects of PTOA

Photon-induced proton knockout from 208Pb

No abstract available

Summary of the OA biomarkers workshop 2009 – biochemical biomarkers: biology, validation, and clinical studies

SummaryOsteoarthritis (OA) biomarkers that can measure and predict the full spectrum of disease progression and outcomes are needed, but few, if any, such biomarkers have been validated for this purpose. The Osteoarthritis Research Society International (OARSI) has organized an OA Biomarkers Global Initiative. As a part of this Initiative, three workshops have been planned to occur over the next 4 years to focus on identifying and removing obstacles to progress in the field and planning the way forward. In addition to OARSI, the National Institute of Arthritis, Musculoskeletal, and Skin Disease, the Arthritis Foundation, the Orthopaedic Research Society, and the American Orthopaedic Sports Medicine Society cosponsored the first meeting April 23–24, 2009. Organizers brought together thought and research leaders in the field, young investigators, biomarkers researchers with insights from other fields, clinical investigators with a responsibility for OA sample and resource management, funding agencies, and commercial entities with an interest in the commercial propagation as well as the application of markers in OA