Combined effects of dynamic tissue shear deformation and insulin-like growth factor I on chondrocyte biosynthesis in cartilage explants
Combined effects of dynamic tissue shear deformation and insulin-like growth factor I on chondrocyte biosynthesis in cartilage explants
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DOI：
10.1016/s0003-9861(03)00195-4
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发表时间：
2003-06-15
影响因子：
3.9
通讯作者：
Grodzinsky, AJ
中科院分区：
文献类型：
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作者：
Jin, M;Emkey, GR;Grodzinsky, AJ
生物物理力和生物化学因素在维持关节软骨的完整性中起着至关重要的作用。在这项研究中，我们探讨了动态组织剪切变形和胰岛素样生长因子I（IGF-I）对天然软骨外植体内软骨细胞基质合成的影响。在0.5-6%应变振幅范围内，在0.1 Hz下的动态组织剪切施加于在无血清培养基中培养的软骨外植体。动态组织剪切超过1.5%的应变幅度显着刺激蛋白质和蛋白多糖的合成，最大值分别为35%和25%，静态控制标本。在没有组织剪切的情况下，IGF-I在100-300 ng/ml范围内的浓度下使蛋白质和蛋白聚糖的合成增加高达两倍。当组织剪切和IGF-I刺激相结合时，基质生物合成水平显着高于单独刺激引起的最大效应。然而，通过双因素方差分析确定，组织剪切力和IGF-I之间没有显著的相互作用。然后，我们量化了动态组织剪切对IGF-I进入软骨外植体和软骨外植体内的运输的影响。向培养基中加入[I-125]IGF-I，在存在和不存在连续动态剪切应变的情况下，直接测量组织内[I-125]IGF-I水平随时间的变化，持续48 h。动态剪切并未改变[I-125]IGF-I摄取到外植体中的速率，表明在所用剪切应变条件下[I-125]IGF-I的对流扩散可忽略不计。这与单轴动态压缩所报告的运输增强形成鲜明对比[1]。综上所述，这些数据表明：（1）组织剪切的刺激作用是通过机械转导途径，而不是通过促进生化因子的转运;（2）软骨细胞可能具有导致代谢活性变化的生物物理和生化因子的互补信号转导途径。(C)2003 Elsevier Science（美国）。All rights reserved.
Biophysical forces and biochemical factors play crucial roles in the maintenance of the integrity of articular cartilage. In this study, we explored the effect of dynamic tissue shear deformation and insulin-like growth factor I (IGF-I) on matrix synthesis by chondrocytes within native cartilage explants. Dynamic tissue shear in the range of 0.5-6% strain amplitude at 0.1 Hz was applied to cartilage explants cultured in serum-free medium. Dynamic tissue shear above 1.5% strain amplitude significantly stimulated protein and proteoglycan synthesis, by maximum values of 35 and 25%, respectively, over statically held control specimens. In the absence of tissue shear, IGF-I augmented protein and proteoglycan synthesis up to twofold at IGF-I concentrations in the range of 100-300 ng/ml. When tissue shear and IGF-I stimuli were combined, matrix biosynthesis levels were significantly higher than the maximal effect caused by either stimulus alone. However, there was no significant interaction between tissue shear and IGF-I as determined by two-way ANOVA. We then quantified the effect of dynamic tissue shear on the transport of IGF-I into and within cartilage explants. [I-125]IGF-I was added to the medium, and the levels of intratissue [I-125]IGF-I were directly measured as a function of time over 48 h in the presence and absence of continuous dynamic shear strain. Dynamic shear did not alter the rate of uptake of [I-125]IGF-I into the explants, suggesting that convective diffusion of [I-125]IGF-I is negligible under the shear strain conditions used. This is in marked contrast to the enhancement of transport reported in response to uniaxial dynamic compression [1]. Taken together, these data suggest that (1) the stimulatory effect of tissue shear is via mechanotransduction pathways and not by facilitated transport of biochemical factors and (2) chondrocytes may possess complementary signal transduction pathways for biophysical and biochemical factors leading to changes in metabolic activity. (C) 2003 Elsevier Science (USA). All rights reserved.