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Yasushi Uchiyama

Publications and source records attributed to Yasushi Uchiyama.

6 recordsLinked to original sources
PubMed2006

c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs.

Although active vitamin D drugs have been used for the treatment of osteoporosis, how the vitamin D receptor (VDR) regulates bone cell function remains largely unknown. Using osteoprotegerin-deficient mice, which exhibit severe osteoporosis due to excessive receptor activator of NF-kappaB ligand/receptor activator of NF-kappaB (RANKL/RANK) stimulation, we show herein that oral treatment of these mice with 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] inhibited bone resorption and prevented bone loss, suggesting that VDR counters RANKL/RANK signaling. In M-CSF-dependent osteoclast precursor cells isolated from mouse bone marrow, 1alpha,25(OH)2D3 potently and dose-dependently inhibited their differentiation into multinucleate osteoclasts induced by RANKL. Among signaling molecules downstream of RANK, 1alpha,25(OH)2D3 inhibited the induction of c-Fos protein after RANKL stimulation, and retroviral expression of c-Fos protein abrogated the suppressive effect of 1alpha,25(OH)2D3 on osteoclast development. By screening vitamin D analogs based on their c-Fos-suppressing activity, we identified a new analog, named DD281, that inhibited bone resorption and prevented bone loss in ovariectomized mice, more potently than 1alpha,25(OH)2D3, with similar levels of calcium absorption. Thus, c-Fos protein is an important target of the skeletal action of VDR-based drugs, and DD281 is a bone-selective analog that may be useful for the treatment of bone diseases with excessive osteoclastic activity.

Animals↗
PubMed2005

Intestinal and renal adaptation to a low-Pi diet of type II NaPi cotransporters in vitamin D receptor- and 1alphaOHase-deficient mice.

Intake of a low-phosphate diet stimulates transepithelial transport of Pi in small intestine as well as in renal proximal tubules. In both organs, this is paralleled by a change in the abundance of the apically localized NaPi cotransporters NaPi type IIa (NaPi-IIa) and NaPi type IIb (NaPi-IIb), respectively. Low-Pi diet, via stimulation of the activity of the renal 25-hydroxyvitamin-D3-1alpha-hydroxylase (1alphaOHase), leads to an increase in the level of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D]. Regulation of the intestinal absorption of Pi and the abundance of NaPi-IIb by 1,25(OH)2D has been supposed to involve the vitamin D receptor (VDR). In this study, we investigated the adaptation to a low-Pi diet of NaPi-IIb in small intestine as well as NaPi-IIa in kidneys of either VDR- or 1alphaOHase-deficient mice. In both mouse models, upregulation by a low-Pi diet of the NaPi cotransporters NaPi-IIa and NaPi-IIb was normal, i.e., similar to that observed in the wild types. Also, in small intestines of VDR- and 1alphaOHase-deficient mice, the same changes in NaPi-IIb mRNA found in wild-type mice were observed. On the basis of the results, we conclude that the regulation of NaPi cotransport in small intestine (via NaPi-IIb) and kidney (via NaPi-IIa) by low dietary intake of Pi cannot be explained by the 1,25(OH)2D-VDR axis.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2004

[ED-71].

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Animals↗
PubMed2003

Specific effects of balance and gait exercises on physical function among the frail elderly.

OBJECTIVE: To evaluate the specific effects of balance and gait exercises among frail elderly individuals. DESIGN: A randomized three-group parallel controlled study. SETTING: Geriatric health services facility in Japan. SUBJECTS: Thirty-four frail elderly subjects attending the care facility were randomized into a control group, an exercise group with emphasis on balance or an exercise group with emphasis on gait re-education. INTERVENTIONS: The two exercise groups received balance or gait exercise for 40 minutes, 2-3 times weekly, for 12 weeks. MAIN OUTCOME MEASURES: One Leg Standing Test, Functional Reach Test, Manual Perturbation Test, Functional Balance Scale, Performance-Oriented Mobility Assessment, Timed 'Up and Go' Test and Stair Climbing/Descending Test. These assessments were performed before and after 12-week intervention. RESULTS: Comparison of the performance before and after intervention demonstrated significant improvement in One Leg Standing Test, Functional Reach Test and Functional Balance Scale in the balance exercise group, and Functional Balance Scale, Timed 'Up and Go' Test and Stair Descending Test showed improvement in the gait exercise group. All test items showed no significant differences in the control groups. Among the three groups, the balance exercise group showed more significant improvement in Functional Balance Scale, and the gait exercise group showed more significant improvement in Performance-Oriented Mobility Assessment than the control group. The balance exercise group showed greater improvement in performance in Functional Reach Test than the gait exercise group. CONCLUSIONS: Balance exercises led to improvements in static balance function, and gait exercises resulted in improvements to dynamic balance and gait functions in the very frail elderly.

Aged↗
PubMed2002

[Relationship between lifestyle activities and physical functions in elderly persons utilizing care facilities].

The purpose of this study was to examine the relationship between outdoor-activity areas and physical functions such as muscle strength, postural balance, gait function, and to identify the physical functions related to accomplishment of outdoor activity in elderly persons utilizing outpatient rehabilitation facilities. Furthermore, we investigated the relationship among physical, social and intellectual activities and physical functions. The subjects were 265 elderly persons (average age: 80.3 +/- 7.0). They were classified into the indoor-activity group, neighborhood outdoor-activity group and long-distance outdoor-activity group, and functional differences among the three groups were examined. The Barthel index, one-leg standing time, timed up-and-go test and performance-oriented mobility assessment were significantly different among the three groups. These results suggested that physical functions have a close relationship with extension of the activity area. Based on 95% confidence intervals, elderly subjects with more than 95 points on the Barthel index seemed able to do neighborhood outdoor activities. Those who can finish timed up-and-go test in less than 18 seconds, and obtain 26 points in performance-oriented mobility assessment may be able to do long-distance outdoor-activities using a bus. Furthermore, it was found that physical function was largely affected by physical activity such as exercise habituation and house keeping. In conclusion the difference of the activity area as well as extended activities of ADL influenced the physical function, which was critical to prevent functional decline in elderly persons.

Activities of Daily Living↗