Clinical calcium最新文献

Rheumatoid arthritis(RA)is one of the systemic autoimmune diseases characterized by progressive joint destruction with chronic synovitis. In the synovium, activated osteoclasts with plenty of inflammatory cytokines and metalloproteinases induce bone and cartilage destruction. Anti-cyclic citrullinated protein antibodies(ACPA)was recognized not only as a diagnostic marker but also as direct inducer of synovitis. In addition, environmental factors and background of daily life also contribute to the pathogenesis of RA, especially smoking and periodontitis are considered to be important factors for disease activities.

Incretins are gastro-intestinal hormones released from enteroendocrine cells in response to food intake. Incretins such as glucose-dependent insulinotropic peptide(GIP)and glucagon-like peptide 1(GLP-1)modulate glucose homeostasis by regulating glucose-dependent insulin release from pancreatic βcells. Dipeptidyl peptidase-4(DPP-4)inhibitors and GLP-1 receptor agonists are incretin-based drugs that have been used for the management of hyperglycemia and obesity in patients with type 2 diabetes mellitus. Although experimental studies have shown that incretin improves bone quality and increases bone mass in rodents, further studies are necessary to clarify the effect of incretin-based drugs on bone mineral density and risk of fractures in humans.

In the past decade, the various types of genetically-encoded optogenetic tools using blue-light sensitive LOV2 domain have been developed and applied in a wide range of areas including neuroscience field. Recently, we succeeded in developing a photoactivatable inhibitory peptide, a genetically-encoded light inducible CaMKⅡ inhibitory peptide. Using this new optogenetic tool, we found that the 1 min of CaMKⅡ activation is sufficient for triggering structural plasticity of synapses(spines)in hippocampal neurons. Furthermore, using passive avoidance test, we found that transient CaMKⅡ activity, but not sustained activity, is only required for fear memory formation/maintenance in amygdala of mice.

Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammation and joint damage that causes significant morbidity and mortality. Rapid and appropriate intervention using disease-modifying anti-rheumatic drugs(DMARDs)is prerequisite to halt joint destruction and long-term functional disabilities. Recent progress in the treatment strategy has brought about paradigm shift for the management of the disease, namely, the combined use of methotrexate, a synthetic DMARD, and a biologic DMARD targeting TNF, IL-6 and T cells has revolutionized treatment of rheumatoid arthritis. Clinical remission is now realistic targets for the treatment, achieved by a large proportion of rheumatoid arthritis patients, which leads to structural remission without damage in bone and cartilage as well as functional remission. Furthermore, orally available small but strong molecules targeting Janus kinase(JAK)are emerging. When DMARDs are prescribed, appropriate selection of DMARDs, adequate screening, regular monitoring and systemic management are required.

Skeletal muscle is the largest tissue in the human body and plays an important role in the regulation of systemic homeostasis and displays remarkable plasticity in their metabolic responses to caloric availability and physical activity. Skeletal muscle maintains muscle mass suitable for the environment according to its own activity state. Skeletal muscles also affect the energy regulation of the whole body by skeletal muscle itself changing muscle fiber composition due to external and internal factors. This review focuses on the transcriptional regulation mechanism of muscle fiber type, which is responsible for overall energy consumption.

Muscle atrophy occurs when glucocorticoid steroids are administered in pharmacological doses or in Cushing syndrome, and such pathological condition is termed as steroid myopathy. Its molecular mechanism is clarified from the study of the gene expression regulation mechanism mediated by steroid receptors in skeletal muscle, progressing to translational research and also addressing the mechanism by which steroids participate in the regulation of whole body energy metabolism via skeletal muscle.

Several population-based studies on osteoarthritis(OA)have been conducted, and its risk factors have been examined. Other prospective studies on knee OA recruited individuals with OA and those without but highly at risk of OA. Osteoarthritis Initiative(OAI)in the United States is one of these studies that aimed to identify biochemical, genetic, and imaging biomarkers for the onset and progression of knee OA. In OAI, a total of 4,796 male and female participants aged 45-79 years at baseline have been followed since 2004. OAI is accumulating data that include participants' knee symptoms, health status, physical examination, physical performance, knee radiographs, knee magnetic resonance images, and biospecimens. Clinical data, images, and image assessments are publically available. Japanese researchers can also utilize these resources for their research.

Osteoarthritis of the knee joints is a disease in which the number of patients is said to be 10 million. The pathomechanism is still unknown, and various researches has been performed. Total knee replacement is a representative treatment. It aims to restore the knee joint function as much as possible. However, the postoperative knee function and the ideal design of implant is not clarified. The latest three-dimensional kinetic analysis method is a completely different approach from the molecular biology queried in this book. It has surprisingly suggested the possibility to elucidate these problems and I would like to introduce some of the results in this chapter.

Induced pluripotent stem (iPS)cells have capacities of self-renewal and pluripotency. We have developed a method to differentiate human iPS cells toward chondrocytes, followed by the creation of cartilage tissue composed of chondrocytes and cartilage extracellular matrix. The mechanism through which tissue transplantation repairs cartilage defects involves the transplant itself constituting the repair tissue. Human iPS cell-derived cartilage has low immunogenicity and can be transplanted in an allogeneic manner. We are conducting pre-clinical tests on iPS cell-derived cartilage to verify efficacy and safety that will act as a basis for clinical tests.

High body weight and high BMI has long been thought to protect against osteoporosis and fragility fractures. However, recent studies indicate that obese individuals fracture risk in some body sites increased with obesity, although it is consistent that obesity remains a protective factor for hip fracture. The association between BMI and fracture risk is complex, differs among fracture sites, and is modified by BMD. FRAX® tool including weight and height is effective to predict fracture even among obesity persons.