Transgenic mouse models for studying the role of cartilage macromolecules in osteoarthritis

The development of transgenic technology has made possible thegeneration of targeted gene-mutated mouse lines suitable foruse in experimental osteoarthritis (OA) research. Transgenicmice harbouring mutations in cartilage collagen types II andIX develop early-onset OA and are therefore promising modelsof age-related OA, even though the mice often show signs ofchondrodysplasia. Also, mouse lines harbouring other engineeredmutations of the extracellular molecules have given rise toearly OA. The molecular background of a few spontaneous mutationsin mice has also been clarified and the characterization ofthe OA phenotype is now in progress. These mutations cause severechondrodysplasia and death in homozygous mice, but the heterozygousoffspring develop the early-onset OA phenotype. Correspondence to: H. J. Helminen, Department of Anatomy, Universityof Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.     

New models of population management for patients with diabetes--using informatics tools to support primary care

Diabetes management continues to fall short of evidence-based goals of care. Population management represents a new approach to diabetes care for large numbers of patients with diabetes cared for within a single clinical system. This method is information intensive and generally requires an advanced informatics infrastructure. While Information Processing is a critical first step in population management, to have a significant impact on disease control population-based intervention must also employ potent Clinical Action tools that lower barriers to effective care. In this review we present two recent population management interventions within our health system that illustrate the principles of Information Processing and Clinical Action in diabetes care.     

Virtual tools for imaging of the thorax.

Helical computed tomography (HCT) allows for volume acquisition of the entire thorax during a single apnoea. Combination of HCT acquisition with synchronous vascular enhancement gives rise to HCT angiography (HCTA). In the last decade, HCT and HCTA have revolutionized the diagnosis of thoracic diseases, modifying many diagnostic algorithms. Because HCT provides for a true volume acquisition free of respiratory misregistration, three-dimensional (3D) rendering techniques can be applied to HCT acquisitions. As these 3D rendering techniques present the HCT information in a different format to the conventional transaxial CT slices, they can be summarized as virtual tools. The purpose of this review is to give the readers the most important technical aspects of virtual tools, to report their application to the thorax, to answer clinical and scientific questions, and to stress their importance for patient management, clinical decision making, and research.     

New pharmacological tools for obesity

Obesity is a multi-factorial, chronic disorder that has reached epidemic proportions in most industrialized countries and is threatening to become a global epidemic. Obese patients are at a higher risk from coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus, certain cancers, cerebrovascular accidents, osteoarthritis, restrictive pulmonary disease, and sleep apnea. Obesity is a particularly challenging clinical condition to treat, because of its complex pathophysiological basis. Indeed, body weight represents the integration of many biological and environmental components. Efforts to develop innovative anti-obesity drugs have been recently intensified. In broad terms, researchers use different distinct strategies: first, to reduce energy intake; second, to increase energy expenditure; third, to alter the partitioning of nutrients between fat and lean tissue. In the present review we concentrate on the first of these strategies, by underlining the new pharmacological tools which are presently studied.     

Ultrasound imaging for the rheumatologist VIII. Ultrasound imaging in osteoarthritis

The present review provides an update of the available data and discusses research issues relating to ultrasound (US) imaging in osteoarthritis (OA). Currently, the principal indications for using US in OA include: delineation of changes within articular cartilage (AC) and demonstration of synovial and adjacent soft tissue pathology together with injection into OA joints under US guidance. US has been proposed as a possible imaging tool for following the progression of OA. The main priorities requiring the attention of researchers include: addressing difficulties surrounding consensus on definitions of pathology in OA, charting the natural history of AC change in site specific OA, investigation of the link between inflammation and OA and the use of three-dimensional (3D) US in OA.     

Bioluminescence imaging of Abeta deposition in bigenic mouse models of Alzheimer's disease

Transgenic (Tg) mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms related to Aβ accumulation. However, assessing disease status in these animals has required time-consuming behavioral assessments or postmortem neuropathological analysis. Here, we report a method for tracking the progression of Aβ accumulation in vivo using bioluminescence imaging (BLI) on two lines of Tg mice, which express luciferase (luc) under control of the Gfap promoter as well as mutant human amyloid precursor protein. Bigenic mice exhibited an age-dependent increase in BLI signals that correlated with the deposition of Aβ in the brain. Bioluminescence signals began to increase in 7-mo-old Tg(CRND8:Gfap-luc) mice and 14-mo-old Tg(APP23:Gfap-luc) mice. When Tg(APP23:Gfap-luc) mice were inoculated with brain homogenates from aged Tg(APP23) mice, BLI detected the accelerated disease onset and induced Aβ deposition at 11 mo of age. Because of its rapid, noninvasive, and quantitative format, BLI permits the objective repeated analysis of individual mice at multiple time points, which is likely to facilitate the testing of Aβ-directed therapeutics.     

Lessons from animal models of osteoarthritis

Characterization of transgenic murine osteoarthritis (OA) models and analysis of anterior cruciate ligament and meniscectomy models in various species, including rodents, has provided insight into pathogenic mechanisms and impact of loading. Development of a transgenic murine OA model by postnatal expression in hyaline cartilage of constitutively expressed human matrix metalloproteinase-13 emphasizes the potential role of this enzyme. On the other hand, collagenase involvement in OA models seems a confined focal process, complicating therapeutic approaches. The potential role of interleukin-1 still needs further confirmation. Apart from destructive cytokines, disturbed growth factor responses seems obvious. Transforming growth factor-beta is a crucial mediator in osteophyte formation, but its role in cartilage destruction has not yet been clarified. Nitric oxide appears involved in chondrocyte apoptosis and blocking of nitric oxide provides protection against joint pathology in OA models. Treatment with a range of disease-modifying drugs showed some efficacy in a number of OA models, but its predictive value for human OA remains obscure.     

The role of imaging in osteoarthritis

Osteoarthritis (OA) is the most prevalent joint disorder with no approved disease-modifying treatment available. The importance of imaging in assessing all joint structures involved in the disease process, including articular cartilage, meniscus, subarticular bone marrow, and synovium for diagnosis, prognostication, and follow-up, has been well recognized. In daily clinical practice, conventional radiography is still the most commonly used imaging technique for the evaluation of a patient with known or suspected OA and radiographic outcome measures are still the only approved end point by regulatory authorities in clinical trials.The ability of magnetic resonance imaging (MRI) to visualize all joint structures in three-dimensional fashion including tissue ultrastructure has markedly deepened our understanding of the natural history of the disease. This article describes the roles and limitations of different imaging modalities for clinical practice and research in OA, with a focus on radiography and MRI and an emphasis on the knee joint.     

骨关节炎治疗新视角

骨关节炎(osteoarthritis,OA)是最常见的一种慢性、进展性关节疾病,也是一种器官系统性疾病.     

骨关节炎影像学研究进展

骨关节炎(osteoarthritis,OA)是最常见的一种关节疾病,以关节软骨损害为主,还可累及软骨下骨、滑膜、韧带、肌腱、关节囊等,甚至影响到整个关节,导致关节软骨发生退变、纤维化、断裂、溃疡等病变。0A主要影响老年人,是老年人肢体残疾和生活水平下降的主要原因。随着世界人口老龄化和肥胖率的增加,0A的患病率越来越高。     

Magnetic resonance imaging of osteoarthritis.

Considering the plethora of imaging protocols, joint-specific orientations, and potential artifacts, the design and interpretation of MR imaging examination is difficult. Like a physical examination, these considerations must be tailored to the specific tissue, joint, and clinical question under consideration. Shortcomings of MR imaging include the lack of consensus among radiologists with respect to which protocols best image articular joints. To date, few prospective studies have been undertaken to assess osteoarthritis by MR imaging. Diagnostic imaging is central to staging the severity of osteoarthritis and assessing the efficacy of therapeutic osteoarthritis. Plain film radiography is insensitive for identifying early changes of osteoarthritis. Tailored MR imaging, producing high spatial and or contrast resolution images, is proving to be an important tool in the early detection and surveillance of osteoarthritis progression. Future therapeutic techniques, such as chondrocyte transplantation, use of growth factors, or cartilage protease inhibitors requires high resolution and volumetric MR imaging studies for accurate identification of focal articular cartilage defects and generalized cartilage loss. Creation of cartilage models by three-dimensional MR image rendering may be helpful for preoperative planning of orthopedic surgical procedures in advanced cases of osteoarthritis. More work needs to be done in high resolution and volumetric MR imaging of articular cartilage. Given the availability of new disease-modifying treatments designed to prevent, delay the progression of, or reverse osteoarthritis, additional prospective MR imaging studies need to be undertaken to improve the reproducibility of MR imaging as a primary outcome measure in the evaluation of osteoarthritis. Interinstitutional standardization of specific MR imaging magnet strengths, surface coils, joint orientations, sequences used, scoring systems and quality assurance methodologies are needed to establish the reproducibility of MR imaging and interpretation for assessment of patients with osteoarthritis.