Reviews & Analysis

With advances in stem cell techniques for the bioengineering and regeneration of musculoskeletal tissues comes added complexity in our understanding of stem cell biology. How will the recent discovery of a novel stem cell subset, termed osteochondroreticular stem cells, contribute to progression in the field?

Despite the successes of biologic therapies in rheumatoid arthritis (RA), not all patients respond to available drugs, and systemic toxicity of some drugs often lead to therapy discontinuation. New developments in polymer–drug conjugates and nanoparticle technology can improve drug efficacy in patients with RA by targeting therapeutic agents to inflamed tissues and extending the half-life of drugs. In this Review, Ferrari and colleagues describe new techniques being explored to improve accumulation of therapeutic agents in the inflamed synovium—a new strategy to boost drug efficacy at disease sites without affecting healthy tissues.

Tendon disorders are common and are a major cause of musculoskeletal pain, but the development of effective therapies requires detailed knowledge of the biology of this mechanosensitive musculoskeletal tissue. As well as providing an overview of tendon physiology and pathology, this article reviews the mechanical and biological factors that contribute to tendon development, homeostasis and repair, drawing on evidence from experimental models and developmental biology.

After outlining the rationale for injecting viable cells into the degenerating intervertebral disc (IVD), Sakai and Andersson provide an overview of basic and preclinical studies as well as ongoing clinical trials of cell therapies for IVD degeneration. Consideration is also given to various barriers to the development of these therapies and possible solutions to overcome such obstacles.

The sensitivity of the long-awaited SLICC classification criteria for systemic lupus erythematosus (SLE) has now been examined in a cross-sectional observational study. Will the new criteria enable advances in the management of SLE?

Targeted therapies and novel strategies to optimize their use enable many patients with RA to achieve a state of low disease activity or even remission, which can be maintained even after tapering or withdrawal of biologic DMARDs. In this article, Smolen and Aletaha review current concepts of RA treatment and the clinical evidence for their effectiveness, in the context of relevant issues such as factors influencing response to therapy, the 'window of opportunity' hypothesis and definitions of treatment targets.

Examination of biopsy-obtained salivary gland tissue provides valuable insights for the diagnosis, classification and treatment of patients with primary Sjögren syndrome. Could the study of biomarkers present in saliva provide a noninvasive alternative?

Genetic factors play an important part in the disease heterogeneity observed in patients with rheumatoid arthritis (RA). Genome-wide association studies (GWAS) have linked common single-nucleotide polymorphisms with the risk of developing RA, but have also highlighted the genetic heterogeneity between Asian and European patients with this disease. In this Perspectives article, the authors discuss recent advances from GWAS in Asian patients with RA, and suggest that better knowledge of the interface between genetic and environmental factors could help our understanding of the disease.

Given the established role of 90 kDa ribosomal S6 kinases (Rsk) in oncogenesis, and the promise of new Rsk-blocking cancer treatments, it is perhaps surprising that Rsk2-mediated inhibition of hyperplasia has now been demonstrated to occur in the arthritic synovium. Does this functional duality make Rsk2 a risky target for the treatment of rheumatoid arthritis?

Recommendations for the use of valgus bracing for knee osteoarthritis are inconsistent. Two new complementary systematic reviews and meta-analyses—concentrating on biomechanical factors and clinical effects, respectively—raise practical issues and suggest future research directions.

Kim et al. hypothesize that IL-21 is crucial to the pathogenesis of primary Sjögren syndrome (pSS), focusing on evidence of an interplay between the innate and adaptive immune responses mediated by the effects of IL-21 on immune cells. This new perspective might ultimately offer insight into novel approaches to the treatment of pSS.

The treatment and study of systemic sclerosis (SSc) is entering a new era with the reporting and preparation of several randomized controlled trials according to an improved understanding of SSc pathogenesis. Advances in trial designs reported in 2014 should now be built upon with further improvements to patient selection to enable targeting of therapies to specific subgroups of patients with SSc.

Optimizing the management of childhood arthritis requires detailed knowledge of the disease in an individual patient. Advances in 2014 show how in-depth genetic studies and insights into immunopathogenesis could translate into clinical biomarkers and, eventually, individualized therapy.

Even though activation of immunity is associated with bone destruction, new mechanisms have been described in 2014 through which immunology-associated pathways can cooperate to support osteogenesis. These advances support the view of the immune system as a central mechanism which can regulate bone homeostasis, regeneration and destruction.

The treatment of juvenile idiopathic arthritis (JIA) has improved markedly in past years, but sustained remission off-medication is still rare. In this Review, Hinze et al. discuss existing treatment approaches and guidelines, with a focus on targeted and patient-centred therapies developed to optimize management strategies for patients with JIA.