Regulation of PTHrP expression by cyclic mechanical strain in postnatal growth plate chondrocytes.
Regulation of PTHrP expression by cyclic mechanical strain in postnatal growth plate chondrocytes.
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DOI：
10.1016/j.bone.2013.06.027
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发表时间：
2013-10
期刊：
影响因子：
4.1
通讯作者：
Tao Xu;Kaixiang Yang;H. You;Anmin Chen;Jiang Wang;Kai Xu;Chen Gong;Jing-fan Shao;Zhongxi Ma;Fengjing Guo;J. Qi
中科院分区：
文献类型：
--
作者：
Tao Xu;Kaixiang Yang;H. You;Anmin Chen;Jiang Wang;Kai Xu;Chen Gong;Jing-fan Shao;Zhongxi Ma;Fengjing Guo;J. Qi
机械负荷已被广泛认为是生长板发育的一个重要调控因素，但这种调控的确切机制仍不完全清楚。在生长板中，甲状旁腺相关蛋白（PTHrP）调节软骨细胞分化和纵向生长。已证实周期性机械应变影响生长板软骨细胞的分化和代谢，而周期性机械应变和PTHrP表达之间的关系尚不清楚。本研究的目的是调查是否短期的周期性拉伸应变调节PTHrP表达在出生后生长板软骨细胞体外，并探讨是否组织的细胞骨架F-actin微丝参与这一过程。为此，我们从2周龄Sprague-Dawley大鼠获得生长板软骨细胞，并使用抗CD 200抗体包被的免疫磁珠分选肥大前和肥大软骨细胞。使分选的软骨细胞在0.5Hz的频率下经受不同幅度和持续时间的循环拉伸应变。我们发现，周期性应变调节PTHrP表达的幅度和时间依赖性的方式。软骨细胞与细胞松弛素D（一种肌动蛋白微扰破坏剂）孵育，阻断了PTHrP表达的诱导。结果表明，短期的周期性拉伸应变诱导PTHrP的表达在出生后的生长板prehypertrophic和肥大的软骨细胞和PTHrP的表达，这些软骨细胞随后可能会影响生长板的发展。这些结果也支持了这样的想法，即细胞骨架F-actin微丝的组织在机械力转导中起着重要的作用。
Mechanical loading has been widely considered to be a crucial regulatory factor for growth plate development, but the exact mechanisms of this regulation are still not completely understood. In the growth plate, parathyroid hormone-related protein (PTHrP) regulates chondrocyte differentiation and longitudinal growth. Cyclic mechanical strain has been demonstrated to influence growth plate chondrocyte differentiation and metabolism, whereas the relationship between cyclic mechanical strain and PTHrP expression is not clear. The objective of this study was to investigate whether short-term cyclic tensile strain regulates PTHrP expression in postnatal growth plate chondrocytesin vitroand to explore whether the organization of cytoskeletal F-actin microfilaments is involved in this process. To this end, we obtained growth plate chondrocytes from 2-week-old Sprague–Dawley rats and sorted prehypertrophic and hypertrophic chondrocytes using immunomagnetic beads coated with anti-CD200 antibody. The sorted chondrocytes were subjected to cyclic tensile strain of varying magnitude and duration at a frequency of 0.5 Hz. We found that cyclic strain regulates PTHrP expression in a magnitude- and time-dependent manner. Incubation of chondrocytes with cytochalasin D, an actin microfilament-disrupting reagent, blocked the induction of PTHrP expression in response to strain. The results suggest that short-term cyclic tensile strain induces PTHrP expression in postnatal growth plate prehypertrophic and hypertrophic chondrocytes and that PTHrP expression by these chondrocytes may subsequently affect growth plate development. The results also support the idea that the organization of cytoskeletal F-actin microfilaments plays an important role in mechanotransduction.