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A potential oncogene that inhibits apoptosis and is called twist (ital) is discussed. A series of modified, replication-deficient retrovirus vectors (MaRX) and packaging cell lines (LinX) that permit high-efficiency gene transfer to a wide range of cell types has been designed. A functional screen for cDNAs able to counteract the proapoptotic effects of the myc (ital) oncogene found two related bHLH family members, Twist and Dermo1. Both proteins inhibited oncogene- and p53-dependent cell death. Twist may have multiple roles in formation of rhabdomyosarcomas.

While research in osteoarthritis has focused on the events that lead to the destruction of articular cartilage, recent evidence suggests that two other components of the joints--bone and synovium--also play key roles in pathogenesis. All three tissues undergo alterations in concert at the structural levels in response to mechanical stress and joint malalignment. Advanced imaging studies such as MRI support this interdependence, revealing the classical changes of joint space narrowing and cartilage degeneration as well as the more recently appreciated bone marrow lesions and synovitis that may correlate with clinical symptoms. Molecular evidence also points to a coordinated release of cytokines and other inflammatory mediators from each of the three tissues together in progression of disease, although we are still in search of biochemical signatures that will predict the subset of patients who progress more quickly--and who will provide key clues to successful molecular targets in future therapies. At this time we lack definitive evidence pointing to which, if any, of the three tissues should serve as the main target for disease modification or structure protection, although most efforts have focused on cartilage. Thus current therapies focus on controlling symptoms, while research efforts search for reliable imaging and molecular biomarkers to help guide future trials of potential disease-modifying agents. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is often a progressive and disabling disease resulting from a combination of risk factors, including age, genetics, trauma, and knee alignment, as well as an imbalance of physiologic processes resulting in inflammatory cascades on a molecular level. The synovium, bone, and cartilage are each involved in the pathophysiological mechanisms that lead to progressive joint degeneration, and, thus, also serve as targets for therapies. Efforts to identify disease-modifying osteoarthritis drugs (DMOADs) have been hampered by several factors, but the focus has now shifted toward the validation of chemical and imaging biomarkers that should aid in DMOAD development. In this review, we summarize current pathological mechanisms occurring in the individual but interconnected compartments of OA joints, as well as discuss related therapeutic interventions that are currently available or on the horizon. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) can be a progressive disabling disease, which results from the pathological imbalance of degradative and reparative processes, with concomitant inflammatory changes. The synovium, bone, and cartilage are each well established sites involved in the pathophysiological mechanisms that lead to progressive joint degeneration. The search for disease-modifying osteoarthritis drugs, DMOADs, has been hampered by several factors, including the variable progression of disease, the lack of specificity and sensitivity of standard radiography, and the fact that the slowing of radiographic progression may not result in corresponding improvement in pain and function. As a result, there is general agreement that development of DMOADs will be facilitated by advances in imaging and the validation of chemical biomarkers. Such biomarkers should be useful tools that will identify patients at risk for disease progression and predict responses to candidate structure-modifying drugs. [ABSTRACT FROM AUTHOR]

While research in osteoarthritis has focused on the events that lead to the destruction of articular cartilage, recent evidence suggests that two other components of the joints-bone and synovium-also play key roles in pathogenesis. All three tissues undergo alterations in concert at the structural levels in response to mechanical stress and joint malalignment. Advanced imaging studies such as MRI support this interdependence, revealing the classical changes of joint space narrowing and cartilage degeneration as well as the more recently appreciated bone marrow lesions and synovitis that may correlate with clinical symptoms. Molecular evidence also points to a coordinated release of cytokines and other inflammatory mediators from each of the three tissues together in progression of disease, although we are still in search of biochemical signatures that will predict the subset of patients who progress more quickly-and who will provide key clues to successful molecular targets in future therapies. At this time we lack definitive evidence pointing to which, if any, of the three tissues should serve as the main target for disease modification or structure protection, although most efforts have focused on cartilage. Thus current therapies focus on controlling symptoms, while research efforts search for reliable imaging and molecular biomarkers to help guide future trials of potential disease-modifying agents.