Hypergravity stimulates osteoblast phenotype expression - A therapeutic hint for disuse bone atrophy

Hypergravity stimulates osteoblast phenotype expression - A therapeutic hint for disuse bone atrophy
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DOI:
10.1196/annals.1329.020
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发表时间:
2004-01-01
期刊:
SIGNAL TRANSDUCTION PATHWAYS, CHROMATIN STRUCTURE, AND GENE EXPRESSION MECHANISMS AS THERAPEUTIC TARGETS
影响因子:
--
通讯作者:
Shinomiya, K
Shinomiya, K
中科院分区:
其他
文献类型:
--
作者:
Morita, S;Nakamura, H;Shinomiya, K

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重力去负荷导致成骨细胞生理活动紊乱。我们研究了适当的超重力水平可以改善易受机械卸载影响的成骨细胞功能的可能性。我们评估了超重力对1 α,25-二羟维生素D-3(VD)诱导的原代大鼠成骨细胞骨钙素表达的影响。将细胞培养板在37 ℃培养箱中以3、6、12、24和48 g离心24 h。通过定量RT-PCR分析mRNA水平。骨钙素和维生素D受体(VD-R)的mRNA水平在12 g时分别增加至1g对照的187%和228%。然而,过度的超重力反过来降低骨钙素的表达。VDND-R通过启动子中的维生素D反应元件增强骨钙素基因表达。骨钙素表达的增加可能反映了VD-R表达的增加。另外,Runx 2,成骨细胞分化的主基因,可能是负责骨钙素诱导,因为Runx 2 mRNA水平也增加到对照组的247%,在12 g。另一种VD诱导的成骨细胞表型碱性磷酸酶在12 g和24 g时也上调。适当水平的超重力增强了VD诱导的骨钙素表达,这是成骨细胞分化的典型表型。这些数据表明,分子特征,以防止废用性骨萎缩的长期卧床患者。
Physiological actions of osteoblasts are disordered by gravity unloading. We investigated the possibility that the appropriate level of hyper-gravity could improve osteoblast functions that are susceptible to mechanical unloading. We evaluated hypergravity effects on the 1 alpha,25-dihydroxyvitamin D-3 (VD)-inducible osteocalcin expression of primary rat osteoblasts. Cell culture plates were centrifuged for 24 h at 3,6, 12,24, and 48g in a 37 degrees C incubator. The mRNA levels were analyzed by quantitative RT-PCR. The mRNA levels for osteocalcin and vitamin D receptor (VD-R) at 12g were enhanced to 187 % and 228% of the 1g control, respectively. However, the excess hypergravity conversely decreased osteocalcin expression. Osteocalcin gene expression was enhanced by VDND-R through the vitamin D-responsive element in the promoter. The increased osteocalcin expression might reflect the augmented VD-R expression. Alternatively, Runx2, a master gene of osteoblast differentiation, might be responsible for the osteocalcin induction, since the Runx2 mRNA levels were also increased to 247% of control at 12g. Another VD-inducible osteoblast phenotype, alkaline phosphatase, was also upregulated at 12g and 24g. The appropriate level of hypergravity enhanced the VD-inducible expression of osteocalcin, a typical phenotype of osteoblast differentiation. These data suggest molecular features to prevent disuse bone atrophy of long-term bed-rest patients.