Cyclic Mechanical Strain Regulates the PTHrP Expression in Cultured Chondrocytes via Activation of the Ca2+ Channel

Cyclic Mechanical Strain Regulates the PTHrP Expression in Cultured Chondrocytes via Activation of the Ca2+ Channel
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DOI:
10.1177/154405910508400111
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发表时间:
2005-01
影响因子:
7.6
通讯作者:
N. Tanaka;S. Ohno;K. Honda;K. Tanimoto;T. Doi;M. Ohno-Nakahara;E. Tafolla;S. Kapila;K. Tanne
N. Tanaka;S. Ohno;K. Honda;K. Tanimoto;T. Doi;M. Ohno-Nakahara;E. Tafolla;S. Kapila;K. Tanne
中科院分区:
医学1区
文献类型:
--
作者:
N. Tanaka;S. Ohno;K. Honda;K. Tanimoto;T. Doi;M. Ohno-Nakahara;E. Tafolla;S. Kapila;K. Tanne

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机械刺激和软骨细胞稳态之间的关联已被报道。然而,PTHrP(甲状旁腺激素相关蛋白)参与软骨细胞代谢的机械调节仍不清楚。我们确定了软骨细胞的机械刺激是否诱导PTHrP的表达,以及PTHrP的机械调节是否依赖于软骨细胞的成熟状态。循环机械应变施加到大鼠生长板软骨细胞在增殖,基质形成,和肥大阶段在30个周期/分钟。循环机械应变显着增加PTHrP的mRNA水平在软骨细胞增殖和基质形成阶段。PTHrP的诱导依赖于增殖阶段的负荷强度。使用特定的离子通道阻滞剂,我们确定,机械诱导的PTHrP抑制硝苯地平,钙通道阻滞剂。这些结果表明,PTHrP的机械诱导可能提供了更大的软骨细胞复制和基质形成,随后会影响软骨形成的环境。
The association between mechanical stimulation and chondrocyte homeostasis has been reported. However, the participation of PTHrP (parathyroid-hormone-related protein) in the mechano-regulation of chondrocyte metabolism remains unclear. We determined whether mechanical stimulation of chondrocytes induces the expression of PTHrP and, further, whether the mechano-modulation of PTHrP is dependent on the maturational status of chondrocytes. Cyclic mechanical strain was applied to rat growth plate chondrocytes at the proliferating, matrix-forming, and hypertrophic stages at 30 cycles/min. Cyclic mechanical strain significantly increased PTHrP mRNA levels in chondrocytes at the proliferating and matrix-forming stages only. The induction of PTHrP was dependent on loading magnitude at the proliferating stage. Using specific ion channel blockers, we determined that mechano-induction of PTHrP was inhibited by nifedipine, a Ca2+ channel blocker. These results suggest that mechanical induction of PTHrP possibly provides the environment for greater chondrocyte replication and matrix formation that would subsequently affect cartilage formation.