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The image shows knee articular cartilage from a chondrocyte-specific Bmal1-knockout mouse. The tissue was stained with safranin O and fast green. Deletion of the transcription factor brain and muscle Arnt-like protein 1 (BMAL1, also known as aryl hydrocarbon receptor nuclear translocator-like protein 1), a core component of the circadian clock, results in the loss of circadian rhythm and leads to degeneration of knee cartilage. The circadian clock controls the rhythmic expression of several hundred genes in cartilage and its function can be affected by inflammation and ageing, both of which are risk factors for osteoarthritis. Studies of the circadian clock will help us better understand cartilage physiology in health and disease.
Image supplied by Dr Michal Dudek from the Faculty of Life Sciences, University of Manchester, Manchester, UK.
Tight regulation of signalling cascades is vital for the correct development and function of bones and joints. A new study suggests that Notch signalling might join the likes of the transforming growth factor superfamily and Wnt signalling cascades as having an important function in joint homeostasis and disease.
Inappropriate activation of Toll-like receptor 4 (TLR4) on resident fibroblasts, through the binding of damage-associated molecular patterns, is a potential driver of fibrosis in systemic sclerosis. New evidence suggests that targeting fibroblast-specific TLR4 or an accessory molecule MD2 could have therapeutic value.
Using mice with targeted deletion of the glucocorticoid receptor, a new study has examined the cell types that mediate the anti-arthritic effects of therapeutic glucocorticoids. Surprisingly, in the serum transfer-induced arthritis model, glucocorticoids target stromal cells rather than immune cells.
Cancer immunotherapies that function as checkpoint inhibitors are an exciting development but are associated with immune-related adverse events that can occur in almost any organ. Among these events are complications that mirror established rheumatic diseases, so oncologists and rheumatologists must work together.
B cell depletion has become standard-of-care for the treatment of ANCA-associated vasculitis, but can more be done to target B cells? In this Review, the authors look beyond rituximab to alternative B cell-targeting therapies and novel therapeutic combinations.
The deposition of calcium-containing crystals can result in various acute and chronic arthropathies. Understanding the biological effects of these crystals and underlying pathogenic mechanisms might inform on the development of future therapeutic strategies for these conditions.
Adult-onset Still’s disease (AoSD) is not easily diagnosed, and treatment options are limited. This Review provides an overview of the disease and its pathogenesis, clinical trial results, therapeutic options and a plan to diagnose and clinically manage these patients.