IL-27 suppresses RANKL expression in CD4+ T cells in part through STAT3.

The receptor activator of NF-κB ligand (RANKL), which is expressed by not only osteoblasts but also activated T cells, plays an important role in bone-destructive diseases such as rheumatoid arthritis. IL-27, a member of the IL-6/IL-12 family cytokines, activates STAT1 and STAT3, promotes early helper T (Th)1 differentiation and generation of IL-10-producing type 1 regulatory T (Tr1) cells, and suppresses the production of inflammatory cytokines and inhibits Th2 differentiation. In addition, IL-27 was recently demonstrated to not only inhibit Th17 differentiation but also directly act on osteoclast precursor cells and suppress RANKL-mediated osteoclastogenesis through STAT1-dependent inhibition of c-Fos, leading to amelioration of the inflammatory bone destruction.

In vitro interaction of high-LET heavy-ion irradiation and chemotherapeutic agents in two cell lines with different radiosensitivities and different p53 status.

Background: To investigate the differences between two rat yolk sac tumor cell lines with different radiosensitivities and p53 status in sensitivity to high-LET heavy-ion beam and in sensitizing effect of etoposide or cisplatin in combination with heavy-ion beam.

Materials And Methods: NMT-1 (wild-type p53 cell) is a parent radiosensitive cell line and NMT-1R (mutant-type p53 cell) is a variant radioresistant cell line. Heavy ion (carbon ion) was accelerated to 290 MeV per nucleon by a heavy-ion medical accelerator in Chiba at National Institute of Radiological Sciences.

[Biochemical markers of bone turnover. New aspect. Bone metabolic markers available in daily practice].

Changes of bone remodeling markers reflect bone growth and bone turnover. Information on bone metabolism can be attained by blood and urine laboratory tests. Recently developed bone specific markers are categorized by bone remodeling process, i.

[Newly developed drugs for osteoporosis in overseas and their future roles for the therapy].

Bisphosphonates are widely used, though gastrointestinal tolerance is a problem on daily administration. Intermittent regimen, from once weekly to once yearly, is now available in overseas and can overcome GI adverse events. New generation of anti-resorptive agents (anti-RANKL antibody and a new SERM, bazedoxifene) are promising and will be soon available for the treatment of osteoporosis.

[Bone quality changes in diabetes].

Diabetes-related bone fragility has recently drawn many researchers' attention. Diabetes would affect bone remodeling by various mechanisms, including deficiency of insulin actions, increased accumulation of advanced glycation end products and microangiopathy. The combination of poor bone quality of microstructure and nanoarchitecture (type I collagen and non-collageous proteins) would reduce bone strength.

[Parathyroid and bone. Evidence and perspective of parathyroid therapy for patients with osteoporosis].

Parathyroid hormone (PTH) is a new management option for patients with osteoporosis. As an anabolic agent that affects bone remodeling and modeling, a novel approach to reducing fracture risk could be considered for patients with severe conditions. A number of trials have shown that increases in spine and hip bone mineral density (BMD), and reduction of fracture risk in postmenopausal women.

[Osteocalcin and bone].

Osteocalcin (OC) is a product of osteoblasts and accumulated in the extracellular matrix of bone. It has been recognized that serum OC is a marker of osteoblast activity, and the levels reflect the rate of bone formation. The present assay system was developed to assess the major circulating forms of intact and the large N-terminal fragments.

Effects of IL-23 and IL-27 on osteoblasts and osteoclasts: inhibitory effects on osteoclast differentiation.

Interleukin (IL)-23 and IL-27 are IL-6/IL-12 family members that play a role in the regulation of T helper 1 cell differentiation. Cytokines are known to be involved in the bone remodeling process, although the effects of IL-23 and IL-27 have not been clarified. In this study, we examined the possible roles of these cytokines on osteoblast phenotypes and osteoclastogenesis.

[Management of osteoporosis in patients with inhaled glucocorticoids].

Inhaled glucocorticoids are the standard of therapy in asthma and are commonly prescribed for chronic obstructive pulmonary disease. Accumulating evidence suggests that the effect of inhaled glucocorticoids on bone is not small, especially in patients taking moderate or high doses for long periods of time. The risk of adverse events is likely to differ between inhaled glucocorticoids.

Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions.

In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-LET feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/microm carbon ions or gamma rays.

Repair kinetics of DNA-DSB induced by X-rays or carbon ions under oxic and hypoxic conditions.

We studied the relation between initial DNA double-strand breaks (DNA-DSB) and the rejoining kinetics of the strand breaks, as well as the OER (oxygen enhancement ratio) after low- and high-LET (linear energy transfer) radiations. CHO cells were exposed to 200 kVp X-rays or 80 keV/microm carbon ions under oxic and hypoxic conditions. DNA-DSB in the cells were analyzed by a static-field gel electrophoresis (SFGE).

Radioprotective activities of beer administration for radiation-induced acute toxicity in mice.

Background And Purpose: We previously found that drinking beer reduces chromosome aberrations in blood lymphocytes that were collected and irradiated in vitro. In this study, we investigated the radioprotective activities of beer-administration for bone marrow and intestine in mice.

Methods: C3H/He female mice received an oral administration of beer, ethanol or saline at a dose of 1 ml/mouse 30 min before whole body irradiation with 137Cs gamma rays or LET 50 keV/microm carbon ions.

Biological gain of carbon-ion radiotherapy for the early response of tumor growth delay and against early response of skin reaction in mice.

The biological effectiveness of carbon ions relative to gamma rays (RBE) was compared between the tumor growth delay and an early skin reaction of syngeneic mice. The RBE was larger for a tumor than skin when irradiated with large doses of high-LET (linear energy transfer) carbon ions. The intra-track damage (a term of a linear quadratic model) of a tumor and skin increased equally with an increase of the LET, while the inter-track damage (beta term) of skin alone increased with the LET.

Differences in pO2 peaks of a murine fibrosarcoma between carbon-ion and X-ray irradiation.

We measured and compared the oxygen partial pressure (pO(2)) profiles in experimental tumors after irradiation with carbon ions and with X-rays. The NFSa fibrosarcomas grown in the hind legs of C3H male mice received isoeffect single doses of carbon ions or X-rays. Coaxial oxygen microelectrodes of high spatial resolution were inserted into the tumor with 20 microm steps by a computerized micromanipulator.

Relative biological effectiveness of 290 MeV/u carbon ions for the growth delay of a radioresistant murine fibrosarcoma.

The relative biological effectiveness (RBE) for animal tumors treated with fractionated doses of 290 MeV/u carbon ions was studied. The growth delay of NFSa fibrosarcoma in mice was investigated following various daily doses given with carbon ions or those given with cesium gamma-rays, and the RBE was determined. Animal tumors were irradiated with carbon ions of various LET (linear energy transfer) in a 6-cm SOBP (spread-out Bragg peak), and the isoeffect doses; i.