The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weightbearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability. Ann Intern Med. 2000;133:635-646. www.annals.org For author affiliations and current addresses, see end of text.

/pdf/osteoarthritis-new-insights-part-1-the-disease-and-its-risk-2p0wtgll5h.pdf

Osteoarthritis: New Insights Part 1: The Disease and Its Risk Factors

Lead Authors Anthony Woolf, Bone and Joint Research Group, Royal Cornwall Hospital, UK; Chair, Global Alliance for Musculoskeletal Health Lyn March, Institute of Bone and Joint Research, University of Sydney, Australia; Chair, Global Alliance for Musculoskeletal Health Surveillance & Information Task Force; Member, International Coordinating Committee Alana Officer, Senior Health Advisor, Department of Ageing and Life Course, WHO International Core Writing Group Marita J Cross*, Institute of Bone and Joint Research, University of Sydney, Australia. Andrew M Briggs*, School of Physiotherapy & Exercise Science, Curtin University, Australia; Arthritis and Osteoporosis Victoria, Australia. Damian Hoy, Global Alliance for Musculoskeletal Health Surveillance & Information Task Force, Secretariat of the Pacific Community. Lidia Sanchez-Riera, Centre on Aging and Mobility, University of Zürich and City Hospital Waid Zurich, Switzerland. Fiona Blyth, Concord Clinical School, University of Sydney, Australia

The World Report on Ageing and Health

The objectives of this study are to review the long-term consequences of injuries to the anterior cruciate ligament and menisci, the pathogenic mechanisms, and the causes of the considerable variability in outcome. Injuries of the anterior cruciate ligament and menisci are common in both athletes and the general population. At 10 to 20 years after the diagnosis, on average, 50% of those with a diagnosed anterior cruciate ligament or meniscus tear have osteoarthritis with associated pain and functional impairment: the young patient with an old knee. These individuals make up a substantial proportion of the overall osteoarthritis population. There is a lack of evidence to support a protective role of repair or reconstructive surgery of the anterior cruciate ligament or meniscus against osteoarthritis development. A consistent finding in a review of the literature is the often poor reporting of critical study variables, precluding data pooling or a meta-analysis. Osteoarthritis development in the injured joints is caused by intra-articular pathogenic processes initiated at the time of injury, combined with long-term changes in dynamic joint loading. Variation in outcome is reinforced by additional variables associated with the individual such as age, sex, genetics, obesity, muscle strength, activity, and reinjury. A better understanding of these variables may improve future prevention and treatment strategies. In evaluating medical treatment, we now expect large randomized clinical trials complemented by postmarketing monitoring. We should strive toward a comparable level of quality of evidence in surgical treatment of knee injuries. In instances in which a randomized clinical trial is not feasible, natural history and other observational cohort studies need to be as carefully designed and reported as the classic randomized clinical trial, to yield useful information.

/pdf/the-long-term-consequence-of-anterior-cruciate-ligament-and-3mhkqdkmu4.pdf

The Long-term Consequence of Anterior Cruciate Ligament and Meniscus Injuries Osteoarthritis

Biomarkers of macrophage-associated inflammatory pathways are associated with OA symptoms and radiographic disease

122 ASSESSMENT OF SERUM AND SYNOVIAL FLUID LEVELS OF IL-1α AND IL-1β IN A MOUSE MODEL OF POST-TRAUMATIC ARTHRITIS

Articular fracture upregulates lipid metabolites in human synovial fluid

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jor.23095

Reply to "Does progranulin account for the opposite effects of etanercept and infliximab/adalimumab in osteoarthritis?" by Wei et al.

127 changes in biomarker levels after acute injury

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