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首页> 外文期刊>International Journal of Molecular Sciences >Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures
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Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures

机译：垂体腺苷酸环化酶激活多肽（PACAP）途径是由机械负荷诱导的，并且减少了软骨微团细胞培养物中的刺猬信号活性。

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no data can be found if PACAP signaling is playing any role during mechanical stress in any tissues, we aimed to investigate its contribution in mechanotransduction during chondrogenesis. Expressions of the mRNAs of PACAP and its major receptor, PAC1 increased, while that of other receptors, VPAC1, VPAC2 decreased upon mechanical stimulus. Mechanical load enhanced the expression of collagen type X, a marker of hypertrophic differentiation of chondrocytes and PACAP addition attenuated this elevation. Moreover, exogenous PACAP also prevented the mechanical load evoked activation of hedgehog signaling: protein levels of Sonic and Indian Hedgehogs and Gli1 transcription factor were lowered while expressions of Gli2 and Gli3 were elevated by PACAP application during mechanical load. Our results suggest that mechanical load activates PACAP signaling and exogenous PACAP acts against the hypertrophy inducing effect of mechanical load.
机译：垂体腺苷酸环化酶激活多肽（PACAP）是一种神经激素，在成熟或发育中的组织的各种应激条件下均发挥保护作用。先前，我们证明了微团细胞培养中鸡肢芽衍生的软骨细胞中存在PACAP信号元件。由于尚无数据显示PACAP信号传导在任何组织的机械应激过程中是否发挥任何作用，因此我们旨在研究其在软骨形成过程中对机械转导的作用。机械刺激后，PACAP及其主要受体PAC1的mRNA表达增加，而其他受体VPAC1，VPAC2的mRNA表达减少。机械负荷增强了X型胶原蛋白的表达，这是软骨细胞肥大分化的标志，PACAP的添加减弱了这种升高。此外，外源性PACAP还阻止了机械负荷引起的刺猬信号的激活：在机械负荷期间，通过PACAP应用，Sonic和Indian Hedgehogs的蛋白水平降低，而Gli1和Gli3的表达降低。我们的结果表明，机械负荷激活PACAP信号传导，外源性PACAP对抗机械负荷对肥大的诱导作用。

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