Current Drug Targets - Volume 11, Issue 5, 2010

Osteoarthritis is among the most common pathological conditions in archeological skeletal collections and is the most frequent musculoskeletal disorder in contemporary populations [1]. Worldwide, symptomatic osteoarthritis affects 9.6% of men and 18.0% of women aged over 60 years (http://www.who.int/chp/topics/rheumatic/en/ WHO Chronic Rheumatic Conditions). As of 2005, 27 million Americans had clinical osteoart Read More

Osteoarthritis, the degeneration of the joints, is the leading source of physical disability with severely impaired quality of life due to pain and loss of joint functioning in industrialized nations. Clinically, degeneration affects mostly the large weight bearing joints of the legs like the hip or the knees, but in principle it can affect any joint of the body. Osteoarthritis represents a disease group with disease subsets that have different und Read More

Osteoarthritis (OA) is a slowly, progressive, ultimately degenerative disorder of movable joints, mainly characterized by joint pain and functional limitation and affecting all joint structures not just articular cartilage, but also the subchondral bone, ligaments, capsule, synovial membrane, and menisci. OA occurs when the equilibrium between breakdown and repair of the joint tissues becomes unbalanced. There are currently n Read More

This narrative review outlines the work done in other fields with regards biomarker validation and qualification and the lessons that we may learn from this experience. Defining a universally agreed upon path for biomarker validation and qualification is urgently needed to circumvent many of the hurdles faced in OA therapeutic development irrespective of whether we are discussing biochemical markers, imaging markers or ot Read More

To date, no targeted treatments for osteoarthritis have been developed. Therefore the challenge for the next years is to find a treatment that may slow down the progression of the disease. Osteoarthritis of the weight-bearing joints, such as knee OA, is more a local mechanical driven disease than a generalized one. To reach a non-vascularised tissue such as the cartilage, local intra-articular administration of drugs should be c Read More

Progressive cartilage degradation is considered a hallmark of osteoarthritis (OA), and as such, methods to inhibit this process have been extensively investigated as potential disease-modifying therapies. However, all tissues of the joint are affected by disease in OA, and it is likely that the pain and disability which are the major clinical symptoms of OA, arrise predominantly from pathology in these extra-cartilaginous str Read More

The great success of targeted biologic therapy against rheumatoid arthritis (RA) in recent years has meant that much research has been devoted to investigating the pathophysiology of osteoarthritis (OA) in the hope of defining novel therapeutic targets. In contrast to RA, with its pannus and erosions, OA has long been thought of as a degenerative disease of cartilage, with secondary bony damage and osteophytes. But in rec Read More

Obesity is one of the main risk factors for osteoarthritis (OA). For many years the association of obesity and OA has been simply attributed to the effects of overload on weight-bearing joints, and epidemiological surveys have shown a strict correlation between an increased body mass index and the severity of knee or hip OA, as well as some relief of pain and disability following weight loss. Instead, there is now a growing bod Read More

In the context of OA disease, NF-κB transcription factors can be triggered by a host of stress-related stimuli including pro-inflammatory cytokines, excessive mechanical stress and ECM degradation products. Activated NF-κB regulates the expression of many cytokines and chemokines, adhesion molecules, inflammatory mediators, and several matrix degrading enzymes. NF-κB also influences the regulated accumulation Read More

Therapeutic alleviation of the pathophysiology of osteoarthritis (OA) is a great and unmet medical challenge. At the basic science level, significant progress has facilitated the identification of distinct pathways and targets which appear to be central to the OA-associated deterioration of articular cartilage. For example, the dysregulated activities of aggrecanases such as ADAMTS-4 and ADAMTS-5, and collagenases such as MMP-1 Read More

Recent evidence from animal experiments and clinical samples points at a role for Wnt-signaling in osteoarthritis (OA) pathology. These pathways are key inducers and regulators of joint development, and are involved in formation of bone, cartilage and also synovium. Disregulation of members from this pathways has been described in OA. This makes the Wnt-family of proteins and signaling pathways an attractive targ Read More

High myopia affects approximately 2% of general population, and is a major cause of legal blindness in many developed countries. Choroidal neovascularization (CNV) is the most common vision-threatening complication of high myopia. Different therapeutic approaches have been attempted such as thermal laser photocoagulation, surgery and photodynamic therapy with verteporfin (PDT). The visual outcome of th Read More

Interleukin (IL)-21, a cytokine mostly produced by activated CD4+ T cells, has been reported to play an important role in the tissue-damaging immune response in various organs. This pathogenic effect is strictly linked to the ability of IL-21 to control the functional activities of multiple immune and non-immune cells. For instance, IL-21 regulates the differentiation and function of effector CD4+ T helper cells, controls act Read More