| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Keiko Nakamura Gakuen University, Dept.of Nutritional Sciences, Professor, 栄養科学部, 教授 (30069786)
TAKAYANAGI Ryoichi Kyushu University, Graduate School of Medicine, Dept.of Geriatric Medicine, Professor, 大学院・医学研究院・老年医学, 教授 (30154917)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
(1)Basic study
Plant-derived monoterpenes, perillyl alcohol, perillic acid and geraniol, were found to enhnance alkaline phosphatase(ALP) activity and inhibit proliferation of the human osteoblast cell line. In addition, the reverse transcription-polymerase chain reaction(RT-PCR) assay revealed that these monoterpenes increased the expression of mRNA for the osteoblat-differentiation markers including ALP in the osteoblast cell line. The role of inhibition of 3-hydroxy-3-methylglutar-yl coenzyme A reductase in promoting bone foemation by these monoterpenes is now under investigation.
To explore whether plant-derived monoterpenes prevent glucocorticoid-induced osteoporosis, one of the most prevalent secondary osteoporosis, we first analysed the molecular mechanism of suppression of bone formation by glucocorticoid. Dexamethasone markedly increased the expression of mRNA for dickkopf-1, an antagonist of Wnt signaling, in primary cultured human osteoblasts. The nuclear translocation of β-ca
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tenin induced by Wnt3a was inhibited by dexamethasone. Thus, it is suggested that glucocorticoid suppresses the canonical Wnt signal, a crucial regulator for bone formation, in cultured human osteoblast.
To investigate the biological effects of plant-derived monoterpenes, we established an animal model of impaired bone formation by feeding the calcium- acid vitamin D-deficient diet to adolescent rats for 40 days. We confirmed both the contents of calcium and phosphorus and the bone mineral density(BMD) were significantly decreased in the femora of the deficient diet-fed rats. The effect of the oral adrministration of plant-derived monoterpenes on the impaired bone formation of the rats is now under investigation.
(2)Clinical study
To determine the lifestyle-related factors associated with bone strength of postmenopausal women, we measured BMD at right radius and urine type I collagen cross-linked N-telopeptide(NTX), a bone resorption marker, and assessed physical status and lifestyle during childhood and present time of pre-and post-menopausal women. The stepwise regression analyses revealed age and timing of menarche as significant predictive factors for decreased BMD and menopause as a significant predictive factor for increased NTX. The habit of skipping breakfast was found to be significant predictive factors for both decreased BMD and increased NTX, resulting in decreased intakes of vegetables and fruits, soybeans, milk products and noodles. Thus, it is suggested that the habitual low vegetables and fruits intake may be a risk factor for impaired bone strength of postmenopausal women. Less
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