ROLE OF 1,25-DIHYDROXYCHOLECALCIFEROL IN GROWTH-PLATE CARTILAGE - INHIBITION OF TERMINAL DIFFERENTIATION OF CHONDROCYTES INVITRO AND INVIVO

被引:55
作者
KATO, Y
SHIMAZU, A
IWAMOTO, M
NAKASHIMA, K
KOIKE, T
SUZUKI, F
NISHII, Y
SATO, K
机构
[1] OSAKA UNIV,FAC DENT,DEPT RADIOL,SUITA,OSAKA 565,JAPAN
[2] CHUGAI PHARMACEUT CO LTD,TOSHIMA KU,TOKYO 171,JAPAN
关键词
D O I
10.1073/pnas.87.17.6522
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The effects of vitamin D metabolites on alkaline phosphatase [ALPase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] activity, a marker of terminal differentiation, in chondrocyte cultures and growth plates in vivo were examined. In cultures of pelleted rabbit growth-plate chondrocytes, 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D3) increased the contents of DNA and macromolecules containing uronic acid (proteoglycans). It also decreased ALPase activity with an ED50 of <1 nM. Other vitamin D3 metabolites, such as 24,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol, had little effect on these biochemical parameters. In rachitic growth plates, the uronic acid content was half that in normal growth plates, whereas ALPase activity was 2.5 times that in normal growth plates. Administration of 1,25-dihydroxycholecalciferol at a low dose (0.1 μg per kg of body weight) to rachitic rats increased the uronic acid content 1.4-fold and decreased ALPase activity by 40%. This compound, like 24,25-dihydroxycholecalciferol (10 μg per kg of body weight), increased the calcium level of the blood. However, administration of 24,25-dihydroxycholecalciferol had little effect on the uronic acid and ALPase contents in growth plates. These observations suggest that 1,25-dihydroxycholecalciferol is a bioactive form of vitamin D that plays an important role in the control of chondrocyte terminal differentiation.
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页码:6522 / 6526
页数:5
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