PDGF-BB, IGF-I and mechanical load stimulate DNA synthesis in avian tendon fibroblasts in vitro
PDGF-BB, IGF-I and mechanical load stimulate DNA synthesis in avian tendon fibroblasts in vitro
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DOI：
10.1016/0021-9290(95)00098-4
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发表时间：
1995-12-01
影响因子：
2.4
通讯作者：
Fischer, T
中科院分区：
文献类型：
--
作者：
Banes, AJ;Tsuzaki, M;Fischer, T
当肌肉收缩以移动四肢或手指时，屈肌腱表面外延和内部隔室中的常驻细胞受到循环机械负荷的影响。肌腱主要是拉伸承载组织，是高度密集的基质，具有不分裂的细胞提供维护功能。然而，当损伤发生时，肌腱细胞被激活的内源性生长因子和来自血小板和血浆的生长因子刺激分裂。我们假设肌腱细胞检测到机械负荷信号，但除非存在活性生长因子，否则不会将这些信号解释为有丝分裂。我们使用了体外机械负荷模型，将循环应变应用于在柔性底培养板上培养的细胞，以验证肌腱细胞除了机械负荷外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合成的假设。此外，我们还证明，在禽类肌腱细胞中，负载因子和生长因子刺激多种蛋白质中酪氨酸残基的磷酸化，包括pp(60)src，一种磷酸化酪氨酸受体蛋白激酶的蛋白激酶。肌腱细胞缺乏对机械负荷的有丝分裂反应可能是调节细胞分裂的调节途径的特征。
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 pp(60)src, 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.