Current Rheumatology Reviews - Volume 2, Issue 1, 2006

Hepatocyte Growth Factor (HGF) is a multifunctional growth factor which, like its receptor c-Met, is widely expressed in osteoarticular tissues. HGF has profound effects on cell motility and differentiation and tissue morphogenesis and angiogenesis. HGF plays an important role in normal bone and cartilage turnover. Changes in HGF/c-Met have also been linked to pathophysiological changes in several bone and joint disorders. H Read More

The protein kinase PKR is a key regulator of stress signalling pathways. We found that the PKR activating protein (PACT) is up-regulated in cartilage at the onset of osteoarthritis. PACT activates PKR in response to various cellular stresses such as TNF-α and IL-1. TNF-α also activates PKR via the sphingolipid second messenger, ceramide. Recent studies have shown that ceramide-induced activation of PKR inhibits protein synthesis Read More

The efficacy of high molecular weight hyaluronan (HA) in reversing cartilage damage in patients with joint degeneration has not yet been clearly demonstrated, although there is compelling evidence of reduction in parameters of pain. The rationales as to why HA may be beneficial to cartilage structure are diverse and are largely based on studies of in vitro models of cartilage damage. However, there are few studies in these Read More

A fine balance between cartilage matrix synthesis and degradation is critical both for the maintenance of articular cartilage function and skeletal development and growth. Disruption of this balance causes abnormalities in skeletal formation and growth and leads to degenerative cartilage diseases, including osteoarthritis and rheumatoid arthritis. Previous studies from this and other laboratories have indicated that Wnt pro Read More

Evaluation of differentially regulated genes is essential for the development of novel therapeutic approaches in multifactorial diseases such as rheumatoid arthritis (RA). The analysis of the pathophysiology of RA requires also a functional understanding of the interactions between different cell types, the cell matrix, intracellular signaling pathways, often also called 'functional genomics', as well as between the different tissue Read More

Rheumatoid arthritis (RA) is characterized by hyperplasia of synovial lining cells, consisting of macrophagelike type A synoviocytes and fibroblast-like type B synoviocytes. Type A synoviocytes, also called intimal macrophages, have been found to be derived from monocyte precursors in the bone marrow. Accordingly, the spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells is accelerated in RA, r Read More

Ankylosing spondylitis (AS) is a potentially disabling rheumatic disease for which no curative treatment has yet been discovered. An extensive computer-based and manual search was undertaken to evaluate the role of microbes in the pathogenesis of AS. All together 147 papers were scrutinised. A total of 24 studies carried out on 1330 AS patients and 1191 healthy controls involving 15 different countries showed signif Read More

Chronic pain has manifested itself as an independent disease. Different molecules acting in nociceptive pathways in the periphery and the nervous system are currently under investigation. Recently the multifunctional protein DREAM (D ownstream Regulatory Element Antagonist Modulator)/calsenilin/KChIP3 has been implicated to play a role in the mechanisms of pain modulation and the hypothesis "No DREAM - Read More

Patients with Systemic Sclerosis [SSc] present great variability in the extent of skin sclerosis, internal organ involvement and prognosis. These aspects have long prompted clinical investigators to differentiate SSc into subsets. The most widely used subsetting schema was proposed by Carwile LeRoy et al. in 1988. The schema differentiates two main subgroups (i.e., limited cutaneous SSc -lcSSc- and diffuse cutaneous SS Read More

Peripheral nervous system dysfunction is well documented in Sjogren's syndrome (SS), whereas central nervous system involvement is a matter of significant controversy. On the other hand, autonomic nervous system (ANS) dysfunction is not even mentioned in extensive reviews of the disease in classic rheumatology textbooks. Despite isolated reports, attention to such involvement in the rheumatologic literature has only been Read More

The deposition of calcium-containing crystals in articular tissues is probably an under-recognized event. Clinical observations indicate that exaggerated and uniquely distributed cartilage degeneration is associated with these deposits. Perhaps the most compelling argument favoring a role for crystals in Osteoarthritis (OA) stems from their in vitro effects on articular tissues. Therapeutic options are limited and of compr Read More

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent self-limited febrile episodes. The hallmarks of a typical attack are fever, peritonitis, pleuritis, arthritis and/or erysipelas-like erythema that resolve within hours or days. The disease primarily affects Sephardic Jews, Armenians, Turks and North African Arabs. The frequency of the attacks can vary and the inciting factors are not always Read More