Clinical calcium最新文献

Bone tissue consist of a wide variety of cells such as osteoclasts, osteoblasts and osteocytes which are involved in bone metabolism, hematopoietic cells which can differentiate and mature in the bone marrow, other mesenchymal cells and nerve cells. Recent advances in "fluorescent imaging technology" have made it possible to observe bone tissue alive. And intravital imaging enable us not only to examine the "morphology" but also to analyze the "dynamics" of the cells. We have improved "two-photon microscope" which can observe deep tissue with minimally invasive manner and have established an imaging method to observe the movement of cells in living bone tissue in real time. In this review, we summarize the methodology of intravital imaging, such as the principle of two-photon excitation microscope, method of in vivo imaging of bone, and analysis of acquired imaging data.

Fluorescent molecules are widely used as a tool to directly visualize target biomolecules in vivo. Fluorescent probes have the advantage that desired function can be rendered based on rational design. For bone-imaging fluorescent probes in vivo, they should be delivered to bone tissue upon administration. Recently, a fluorescent probe for detecting osteoclast activity was developed. The fluorescent probe has acid-sensitive fluorescence property, specific delivery to bone tissue, and durability against laser irradiation, which enabled real-time intravital imaging of bone-resorbing osteoclasts for a long period of time.

In bone tissues, there are various kinds of cell types, such as osteoclasts, osteoblasts, monocytes, granulocyte, lymphocytes, mesenchymal cells and hematopoietic stem cells. They form a network with each other, and play critical roles in our life activities. The recent development of intravital two-photon imaging has enabled us to visualize the in vivo behavior of bone marrow cells in living bone tissues. This technique facilitates investigation of cellular dynamics in the physiology and pathogenesis of bone disorders in vivo, and would thus be useful for evaluating the efficacy of novel drugs. In this review, we summarize the basis of intravital bone imaging, and also discuss its further application.

The neuromuscular junction(NMJ)is the synapse between a motor neuron and the skeletal muscle that is essential for muscle contraction. Impairments at the NMJ lead to neuromuscular-transmission pathologies characterized by fatigable muscle weakness. Muscle-specific receptor tyrosine kinase MuSK plays key roles in NMJ formation. Over the past decade, studies examining the NMJ formation signals have identified molecules involved in the signaling pathways and have promoted a better understanding of characteristic molecular mechanisms for MuSK activation. Unlike many other receptor tyrosine kinases, MuSK is regulated by the cytoplasmic activator Dok-7 in addition to the extracellular activator agrin. It is well established that all of these molecules are indispensable in the formation and maintenance of the NMJ. In this chapter, we review molecular signaling, particularly MuSK signaling, in the formation of the NMJ and the altered molecular signaling associated with neuromuscular disorders.

Decline of homeostasis in musculoskeletal locomotive organs such as bone and muscle with age leads to age-related diseases such as osteoporosis and muscle atrophy. To date, various findings underlying the pathogenesis of these tissues were accumulated. In this review, we discuss regarding the recent advances in the findings in the treatment for osteoporosis and the strategy for muscle atrophy, and our recent findings on the mechanisms underlying these diseases.

Osteocytes have several functions such as sensing mechanical load to bone and regulating osteoclastic bone resorption. In addition, osteocytes secrete several humoral factors that affect bone and other organs. FGF23 produced by osteocytes works as a hormone that reduces serum phosphate level. Sclerostin suppresses bone formation by inhibiting Wnt signals. Drugs that inhibit the activities of these factors are now under investigation as new therapeutic measures.

Rheumatoid arthritis(RA)has been a disease of unknown cause for many years. However, the etiology is becoming obvious due to the use of biological products in recent years, arthritis model mice in basic immunology and genome wide analysis in genetics etc. In particular, the knowledge of what is effective and what is not effective for biological products directly reveals the pathology of RA. It has also been found that the cytokine dependence of arthritis model mice and RA is not necessarily the same. It is pointed out that the difference may be derived from the presence of anti-citrullinated protein antibody(ACPA). Studies of immune responses against self antigens such as citrullinated protein will provide a clue to elucidate the pathogenesis of RA. Further analysis of genetic polymorphism and epigenome in combination with human immunity is expected to promote understanding of RA.

It is well known that the rise of FSH is a hallmark of menopause associated with osteoporosis and visceral adiposity. Recent days, Zahidi's group reported that blocking FSH signals prevents bone loss in ovariectomized mice by inhibiting bone resorption and stimulating bone synthesis. The same research group also showed that blocking FSH action reduces body fat volume by promoting beige fat thermogenesis. These findings open new doors for novel and complementary treatments addressing post-menopausal osteoporosis and metabolic diseases.

Diabetes is associated with increased fracture risk, involving a variety of factors. Besides poor glycemic control itself, some glucose-lowering agents are also associated with increased fracture risk. Thiazolidinediones increase fracture risk probably through inhibition of bone formation as well as increased resorption leading to decreased BMD. Sodium-glucose cotransporter(SGLT)-2 inhibitors have been reported to decrease BMD and increase fracture risk. However, the class effect of SGLT-2 inhibitors on bone metabolism remains to be established. In diabetic patients, especially in those with high fracture risk such as postmenopausal women, careful selection of glucose-lowering agents as well as appropriate and timely intervention for osteoporosis is necessary.

It is well established that patients with maintenance hemodialysis increased fracture rates compared with the general population, incident hip fractures are associated with substantial morbidity and mortality. To prevent fractures in hemodialysis patients, bone turnover markers are useful as well as measurement of bone mineral density.