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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Regulation of growth plate chondrocytes by 1,25-dihydroxyvitamin D3 requires caveolae and caveolin-1.
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Regulation of growth plate chondrocytes by 1,25-dihydroxyvitamin D3 requires caveolae and caveolin-1.

机译：1,25-二羟基维生素D3调节生长板软骨细胞需要小窝和小窝-1。

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摘要

We examined the role of caveolae and caveolin-1 in the mechanism of 1alpha,25(OH)(2)D(3) action in growth plate chondrocytes. We found that caveolae are required for rapid 1alpha,25(OH)(2)D(3)-dependent PKC signaling, and caveolin-1 must be present based on studies using chondrocytes from Cav-1(-/-) mice. INTRODUCTION: 1,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] regulates endochondral ossification in part through membrane-associated mechanisms, including protein kinase C (PKC) signaling activated by a membrane-associated 1alpha,25(OH)(2)D(3)-binding protein, ERp60. We tested the hypothesis that caveolae are required for 1alpha,25(OH)(2)D(3) action and play an important role in regulating chondrocyte biology and growth plate physiology. MATERIALS AND METHODS: Rat costochondral chondrocytes were examined for caveolae by transmission electron microscopy of cultured cells and of cells in situ. Western blots and confocal microscopy were used to detect caveolae proteins including caveolin-1 (Cav-1) and1alpha,25(OH)(2)D(3) receptors. Caveolae cholesterol was depleted with beta-cyclodextrin (CD) and effects of 1alpha,25(OH)(2)D(3) on PKC, DNA synthesis, alkaline phosphatase, and proteoglycan production determined. Chondrocytes from Cav-1(-/-) and C57BL/6 wildtype mice were also treated with 1alpha,25(OH)(2)D(3). Epiphyses and costochondral junctions of 8-week-old male Cav-1(-/-) and wildtype mice (N = 8) were compared by histomorphometry and microCT. Data were analyzed by ANOVA and Bonferroni for posthoc comparisons. RESULTS: Growth zone chondrocytes had caveolae and Cav-1, -2, and -3. Resting zone chondrocytes, which do not exhibit a rapid 1alpha,25(OH)(2)D(3)-dependent increase in PKC activity, also had these caveolins, but caveolae were larger and fewer in number. ERp60 but not VDR co-localized with Cav-1 in plasma membranes and in lipid rafts. CD-treatment blocked 1alpha,25(OH)(2)D(3) effects on all parameters tested. The Cav-1(-/-) cells did not respond to 1alpha,25(OH)(2)D(3), although 1alpha,25(OH)(2)D(3) increased PKC, alkaline phosphatase, and [(35)S]-sulfate incorporation in wildtype C57BL/6 cells. Histology and microCT showed that Cav-1(-/-) growth plates were longer and had more hypertrophic cells in each column. Growth plate changes were reflected in the metaphysis. CONCLUSIONS: The membrane-mediated effects of 1alpha,25(OH)(2)D(3) require caveolae and Cav-1, and Cav-1 deficiency results in altered growth plate physiology.
机译：我们检查了caveolae和caveolin-1在生长板软骨细胞中的1alpha，25（OH）（2）D（3）作用机制中的作用。我们发现快速1alpha，25（OH）（2）D（3）依赖的PKC信号所必需的小窝，并且基于使用来自Cav-1（-/-）小鼠的软骨细胞的研究，小窝1必须存在。简介：1,25-二羟基维生素D（3）[1alpha，25（OH）（2）D（3）]部分通过膜相关机制调节软骨内骨化，包括被膜激活的蛋白激酶C（PKC）信号传导。相关的1alpha，25（OH）（2）D（3）结合蛋白ERp60。我们测试的假设，小窝需要1alpha，25（OH）（2）D（3）的作用，并在调节软骨细胞生物学和生长板生理中起重要作用。材料与方法：用透射电镜对培养的细胞和原位细胞进行透射电镜观察。 Western印迹和共聚焦显微镜用于检测caveolae蛋白，包括caveolin-1（Cav-1）和1alpha，25（OH）（2）D（3）受体。小窝胆固醇被β-环糊精（CD）耗尽，并确定了1alpha，25（OH）（2）D（3）对PKC，DNA合成，碱性磷酸酶和蛋白聚糖生产的影响。来自Cav-1（-/-）和C57BL / 6野生型小鼠的软骨细胞也用1alpha，25（OH）（2）D（3）处理。通过组织形态计量学和microCT比较了8周龄雄性Cav-1（-/-）和野生型小鼠（N = 8）的骨和肋软骨交界处。数据通过ANOVA和Bonferroni进行了事后比较分析。结果：生长区软骨细胞具有小窝和Cav-1，-2和-3。静息区软骨细胞，不表现出快速的1alpha，25（OH）（2）D（3）依赖性PKC活性的增加，也有这些小窝蛋白，但小窝较大且数量较少。 ERp60但不是VDR与Cav-1共定位在质膜和脂质筏中。 CD处理可阻止1alpha，25（OH）（2）D（3）对所有测试参数的影响。尽管1alpha，25（OH）（2）D（3）增加了PKC，碱性磷酸酶和[[]，Cav-1（-/-）细胞对1alpha，25（OH）（2）D（3）没有反应。 （35）S]-硫酸盐掺入野生型C57BL / 6细胞中。组织学和microCT显示，Cav-1（-/-）生长板更长，每列中的肥大细胞更多。生长板的变化反映在干physi端。结论：1alpha，25（OH）（2）D（3）的膜介导作用需要小窝和Cav-1，而Cav-1缺乏会导致生长板生理变化。

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