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血小板衍生生长因子-BB、胰岛素样生长因子-I和机械负荷在体外刺激禽腱成纤维细胞中的DNA合成。

PDGF-BB, IGF-I and mechanical load stimulate DNA synthesis in avian tendon fibroblasts in vitro.

作者信息

Banes A J, Tsuzaki M, Hu P, Brigman B, Brown T, Almekinders L, Lawrence W T, Fischer T

机构信息

Department of Surgery, University of North Carolina, Chapel Hill 27599-7050, USA.

出版信息

J Biomech. 1995 Dec;28(12):1505-13. doi: 10.1016/0021-9290(95)00098-4.

DOI:10.1016/0021-9290(95)00098-4
PMID:8666590
Abstract

Resident cells in the surface epitenon and internal compartment of flexor tendons are subjected to cyclic mechanical load as muscle contracts to move limbs or digits. Tendons are largely tensile load bearing tissues and are highly matrix intensive with nondividing cells providing maintenance functions. However, when an injury occurs, tendon cells are stimulated to divide by activated endogenous growth factors and those from platelets and plasma. We hypothesize that tendon cells detect mechanical load signals but do not interpret such signals as mitogenic unless an active growth factor is present. We have used an in vitro mechanical load model, application of cyclic strain to cells cultured on flexible bottomed culture plates, to test the hypothesis that tendon cells require platelet-derived growth factor (PDGF-BB) and insulin-like growth factor-I (IGF-I) in addition to mechanical load to stimulate DNA synthesis. In addition, we demonstrate that in avian tendon cells, load and growth factors stimulate phosphorylation of tyrosine residues in multiple proteins, including pp60src, a protein kinase that phosphorylates receptor protein tyrosine kinases. A lack of mitogenic responsiveness to mechanical load alone by tendon cells may be a characteristic of a regulatory pathway that modulates cell division.

摘要

随着肌肉收缩以移动肢体或手指,屈肌腱表面腱鞘和内部腔室中的驻留细胞会受到周期性机械负荷。肌腱主要是承受拉伸负荷的组织,高度富含基质,其中不分裂的细胞发挥维持功能。然而,当损伤发生时,肌腱细胞会被内源性生长因子以及来自血小板和血浆的生长因子激活而进行分裂。我们假设肌腱细胞能检测机械负荷信号,但除非存在活性生长因子,否则不会将此类信号解读为促有丝分裂信号。我们使用了一种体外机械负荷模型,即对培养在柔性底部培养板上的细胞施加周期性应变,以检验以下假设:除了机械负荷外,肌腱细胞还需要血小板衍生生长因子(PDGF - BB)和胰岛素样生长因子 - I(IGF - I)来刺激DNA合成。此外,我们证明在禽类肌腱细胞中,负荷和生长因子会刺激多种蛋白质中酪氨酸残基的磷酸化,包括pp60src,一种可使受体蛋白酪氨酸激酶磷酸化的蛋白激酶。肌腱细胞对单独机械负荷缺乏促有丝分裂反应可能是调节细胞分裂的调控途径的一个特征。

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