News & Views in 2018

Vitamin D is important for skeletal metabolism and calcium homeostasis, but conflicting evidence exists as to whether vitamin D supplementation has a protective effect on musculoskeletal outcomes. Do the results of a new meta-analysis bring clarity or increase confusion?

Shifts in cellular metabolism are central to activation, differentiation and proliferation of inflammatory cells and can contribute to the pathogenesis of inflammatory diseases. Integrating metabolomics data with other omics data is a major challenge but might enable clinicians to stratify stages of disease and response to therapy in patients with rheumatoid arthritis.

‘Patient-centered’ research has traditionally meant that researchers and clinicians design trials for the benefit of patients. By contrast, patients today are central to study design and reporting outcomes, and new research agendas recognize that patients can point the way to research questions and how to address them.

Despite the previous identification of genes involved in the treatment response to TNF inhibition in rheumatoid arthritis, no genetic biomarkers are currently used in clinical decision-making. Might the heterogeneous nature of the disease activity score, which is often used as the outcome measure in genetic studies, partly explain this gap?

The search for the identity of skeletal stem cells has reached a point at which skeletogenic cell populations with self-renewing capacity can be enriched and studied in detail. These advances provide new hope for skeletal regenerative medicine.

Gasdermin D is a pore-forming protein that can cause pyroptosis, a form of inflammatory cell death. New research indicates that the pores generated by gasdermin D can also promote the formation of neutrophil extracellular traps, potentially opening new therapeutic avenues for the treatment of inflammatory diseases.

A variety of comorbidities of gout exist, but most of these associations are not causally linked. Mendelian randomization analysis of genome-wide association study data now suggests that iron overload might increase serum uric acid levels and hence the risk of gout flares.

Current guidelines for the treatment of osteoarthritis involve exercise and lifestyle modifications as well as pharmaceutical therapeutics for effective pain management. Is this message reaching patients, and are they exercising enough?

Seropositive RA can present with two different types of autoantibodies that have distinct features: anti-citrullinated protein antibodies (ACPAs) and rheumatoid factors (RFs). With a single-cell approach, researchers provide evidence that the underlying B cell subsets of these autoantibody specificities develop in parallel by different mechanisms.

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.

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.

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.

Stimulator of interferon genes (STING), an important component of the cytosolic DNA sensing pathway, is an attractive therapeutic target for ameliorating interferon-driven systemic inflammation. New findings are shedding light on how STING functions and on a strategy to target STING therapeutically.

Mental health symptoms are a common and functionally impairing feature of rheumatoid arthritis, and increasingly seem to represent an integral part of the inflammatory process. Could treatment with DMARDs affect physical as well as mental health outcomes?

Combining TNF inhibition with methotrexate treatment is an effective therapeutic approach for patients with rheumatoid arthritis and reduces the likelihood of the patient developing ‘resistance’ to the TNF inhibitor. But how does methotrexate suppress the production of anti-drug antibodies and how can we tell which patients will develop resistance?

Large-scale genetic studies have highlighted the retinoic acid pathway as a contender in the pathogenesis of hand osteoarthritis. Functional studies are offering further insights into the role of retinoic acid that might translate into future therapies.

A variety of biologic DMARDs now exist for the treatment of rheumatoid arthritis, but we don’t really know how these drugs function in vivo. Can time-lapse intravital imaging distinguish the modes of action of DMARDs by comparing response to joint destruction in mouse models of arthritis?

Some patients with psoriatic arthritis are refractive to one biologic therapy but not to others, and a strategy for selecting the right therapy for each patient is needed. The findings of a new study highlight the potential benefit of stratifying patients by their immunophenotype to select the optimal biologic to use.

A new epidemiological study suggests that only half of patients with hyperuricaemia will go on to develop gout. If ‘the glass is only half-full’, then is hyperuricaemia the most important risk factor for the development of gout?

Poor medication adherence and depression interfere with the management of patients with systemic lupus erythematosus, especially adolescent and young adult patients. For patients for whom clinic visits and education programs fail to improve adherence, novel social media-based interventions are demonstrating the ability to increase patient agency, self-efficacy, and adherence.