Abstracts


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Adipokines in Arthritis: New Kids on the Block
Odile Gabay and Francis Berenbau

Along with its capacity to store energy, the white adipose tissue is a source of cytokines, called “adipocytokines” or “adipokines”, acting by paracrine, autocrine and systemic pathways. However, it is noteworthy that the source of these adipokines in physiological and/or pathological conditions is not restricted to the adipose tissue. The modulation of immunological and inflammatory pathways by adipokines has been extensively studied in the last ten years. This systematic literature review focuses on the role of leptin, adiponectin, resistin and visfatin in arthritis. Although their roles need to be clarified, these adipokines will soon be pivotal to the diagnosis, the prognosis and the pharmacological approaches of rheumatoid arthritis and osteoarthritis.


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Transport properties of cartilaginous tissues.
Alicia R. Jackson and Wei Yong G

Cartilaginous tissues, such as articular cartilage and intervertebral disc, are avascular tissues, which rely on transport for cellular nutrition. Comprehensive knowledge of transport properties in such tissues is therefore necessary in the understanding of nutritional supply to cells. Furthermore, poor cellular nutrition in cartilaginous tissues is believed to be a primary source of tissue degeneration, which may result in osteoarthritis (OA) or disc degeneration. In this minireview, we present an overview of the current status of the study of transport properties and behavior in cartilaginous tissues. The mechanisms of transport in these tissues, as well as experimental approaches to measuring transport properties and results obtained are discussed. The current status of bioreactors used in cartilage tissue engineering is also presented.
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Interstitial lung disease in idiopathic inflammatory myopathy
Guest Editor: Eric Matteson

The issue of interstitial lung disease (ILD) often comes up in the clinical practice of rheumatology. The etiology, risk factors, exacerbating factors, and treatment of ILD in the context of autoimmune diseases is the topic of this month's Current Rheumatology Reports. As laid out by Dr. Matteson in his editorial, research in this field is complicated by the lack of standardized criteria for the diagnosis and the lack of widely accepted outcome measurements. The international CTD-ILD interest group is trying to address this problem by developing standardized clinical trial assessments. In a thought provoking piece in this issue of the journal, this group has laid out their vision of how to achieve such a standardization. Additionally, superb reviews on ILD in scleroderma, SLE, RA, Sjogren's and myositis are presented here. The reader will also find useful insights in the review of The idiopathic interstitial pneumonias and CTD associated ILD by Swigris and colleagues.

It has been our goal at the journal to provide a forum for thought leaders to share their insights on the state of their field of expertise. Indeed, we have achieved this goal spectacularly in this issue of the journal.

Swamy Venuturupalli, M.D., F.A.C.R.
Asst. Clinical Prof. of Medicine-UCLA
Attending physician-Cedars Sinai Medical Center,
Los Angeles, CA
USA

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Rheumatoid foot and ankle surgery
Claire M. Capobianco, Crystal L. Ramanujam and Thomas Zgonis.

Rheumatoid arthritis is a common and disabling condition which can be effectively managed through a multidisciplinary approach. A review of the etiology, pathophysiology, clinical presentation, diagnosis and treatment is presented, followed by a discussion focused on the disease presentation and management in the foot and ankle. Conservative care options, perioperative considerations and surgical treatment options for rheumatoid deformity in the foot and ankle are discussed.


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Osteoclast apoptosis in rheumatic diseases characterized by a high level of bone resorption (osteoporosis, rheumatoid arthritis, myeloma and paget's disease of bone)
Sophie Roux and Jacques P. Brown

The resorption and formation of bone are closely linked during bone remodeling. The cessation of bone resorption precedes bone formation, and is characterized by osteoclast apoptosis. The two most common apoptotic pathways consist of the activation of one of the membrane death receptors, including Fas that binds FasL, and the TRAIL receptors that bind TRAIL (TNF-Related Apoptosis-Inducing Ligand), and the mitochondrion-activated pathway involving members of the Bcl-2 family. Apoptosis occurs in osteoclasts, and is an important point of control of bone resorption. M-CSF and RANKL, the two critical factors involved in osteoclast formation and activation, are osteoclast survival factors and down-regulate osteoclast apoptosis. The regulation of this process may be important in controlling bone homeostasis, and could be altered in vivo under conditions characterized by a high level of osteoclast formation. Bone diseases, such as osteoporosis, malignant osteolysis, and Paget’s disease of bone, are characteristically associated with bone hyper-resorption, as rheumatoid arthritis where peri-articular or subchondral bone resorption may occur. There is now increasing evidence suggesting that changes in the regulation of osteoclast death may contribute to these clinically important bone diseases, and that the induction of osteoclast apoptosis is a potential therapeutic tool for treating them..


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Benzo[a]pyrene toxicity and inflammatory disease
Shigeyuki Uno and Makoto Makishima

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon found in cigarette smoke, grilled meats and byproducts of industrial incineration. BaP exposure through cigarette smoking has been implicated in the pathogenesis of lung and head-and-neck cancers and atherosclerosis. BaP inhalation activates the aryl hydrocarbon receptor (AHR), a transcription factor that induces expression of genes involved in xenobiotic metabolism. BaP can be metabolized to active compounds that form DNA adducts and induce the production of reactive oxygen species in cells, leading to inflammatory cytokine production. Polymorphisms of cytochrome P450 enzymes that are induced by AHR and function in BaP metabolism have been reported to confer increased risk of rheumatoid arthritis in Asian populations. AHR induces T cell differentiation to both immunoregulatory and autoimmune/inflammatory lineages. Dynamic metabolic activation of BaP and cell type-specific AHR activation may influence AHR-regulated immune responses. An improved understanding of AHR function should provide pharmacologic approaches to BaP detoxification useful in the prevention of diseases associated with environmental pollutants, such as rheumatoid arthritis


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Exercise for fibromyalgia pain: A meta-analysis of randomized controlled trials
Judith Ramel, Raveendhara Bannuru, Marcie Griffith and Chenchen Wang.

Objective: To systematically review the efficacy of exercise interventions on pain relief in patients with fibromyalgia (FM).

Methods: We performed a comprehensive search of 8 western databases and reference lists through March 2009. We included randomized controlled trials (RCTs) with pain as an endpoint, measured by the Fibromyalgia Impact Questionnaire (FIQ) or a visual analogue scale (VAS). The exercise treatments were compared with a no-exercise control group. Study quality was assessed by the Jadad scale. We calculated effect sizes to assess the magnitude of treatment effect, and meta-analyzed for overall effect.

Results: Forty-five studies were critically appraised for effects on pain. Ten RCTs published between 1992 and 2008, conducted in Europe and North America met eligibility criteria with 767 participants (98% women). Mean age was 47 years and mean symptom duration was 10 years. The meta-analysis results showed that 6 to 24 weeks of aerobic, strength training, pool and multi-component exercise had a statistically significant decrease in pain outcomes versus education, usual care and non-exercise controls. The pooled effect size was 0.45 (95% Confidence Interval, 0.09 to 0.80).

Conclusion: Physical exercise may have positive effects on pain reduction in patients with FM. Long-term, rigorous and well-controlled randomized trials are warranted.


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Role of biomechanical force in stem cell-based therapy for cartilage repair
Bindu Bahuleyan, Herman S. Cheung and C.-Y. Charles Huang.

The regeneration of damaged cartilage due to injuries and diseases is a major goal for the future. Cartilage has limited healing capacity. There have been a number of studies shown to induce cartilage regeneration both in vitro and in vivo. Yet we are far from obtaining regenerated cartilage that has the properties similar to the native cartilage. Chondrogenesis of mesenchymal stem cells (MSCs) can be induced by biophysical and biochemical factors. This review article focuses on the recent studies and their findings on the role of mechanical loading on inducing chondrogenesis of MSCs. Previous studies have demonstrated promising results on mechanical stimulation of MSC chondrogenesis. More studies are needed to provide optimal conditions for mechanical stimulation of MSC chondrogenesis and a better understanding in mechanisms behind it. Therefore, it will help to develop new strategies for cartilage repair using MSC-based therapies such as cell transplantation and cartilage tissue engineering.


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Osteoarthritis: The need for innovative therapeutic interventions
Ann K. Rosenthal

Osteoarthritis is the most common form of arthritis in adults and is projected to increase in prevalence as the population ages. This review summarizes the currently available management strategies for osteoarthritis, the rationale behind their use, and the current data supporting their efficacy. It underscores the need for new and effective therapies for this common and disabling condition.