| Project/Area Number |
11671842
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
NOSHIRO Mitsuhide Hiroshima Univ., Facultyl of Dentistry, Associate Prof., 歯学部, 助教授 (00144858)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | chondrocyte / retinoic acid / RBP / PTH / cAMP / hedgehog |
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| Research Abstract |
The following results were obtained to clarify the role of retinoic acid and PTH as the modulators in the growth and development of chondrocytes.
(1) Parathyroid hormone (PTH) and dibutyryl cAMP ((Bu) 2cAMP) induced the expression of plasma retinol-binding protein (RBP) in the conditioned media of rabbit growth plate chondrocyte cultures.
(2) Northern blot analysis showed that PTH, parathyroid hormone-related peptide (PTHrP) and (Bu) 2cAMP increased the RBP mRNA level in chondrocyte cultures. Further, both PTH and (Bu) 2cAMP markedly induced the expression of RBP mRNA indicating a pretranslational regulation. The level of the mRNA expression induced by PTH, PTHrP and (Bu) 2cAMP was as high as that by retinoic acid (RA).
(3) Both RBP and PTH/PTHrP inhibited the dedifferentiative activity of RA on growth plate chondrocytes. These results demonstrate that chondrocytes synthesize and secrete RBP in vivo and in vitro, and suggest that PTH/PTHrP naodulates the effect of RA by means of RBP production in chondrocytes.
(4) RA and bone morphogenetic protein-2 (BMP-2) enhanced Indian hedgehog (Ihh) mRNA expression, whereas PTH/PTH-related peptide (PTHrP) markedly suppressed Ihh expression.
(5) Cycloheximide blocked the up-regulation of Ihh by RA, indicating the requirement of de novo protein synthesis for this stimulation. These findings suggest that RA is involved in the up-regulation of Ihh during endochondral bone formation.
(6) PTH rapidly abolished the mRNA expression of Ihh. The inhibition of Ihh expression by PTH (1-84) did not require de novo protein synthesis. The direct inhibitory action of PTH/PTHrP on Ihh appears to be a negative feedback mechanism that prevents excess PTHrP accumulation in cartilage.
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