Holmvall K, Camper L, Johansson S, Kimura J H, Lundgren-Akerlund E
Department of Cell and Molecular Biology, University of Lund, Sweden.
Exp Cell Res. 1995 Dec;221(2):496-503. doi: 10.1006/excr.1995.1401.
Mechanical stress is an important regulator of chondrocyte functions but the mechanisms by which chondrocytes sense mechanical signals are unknown. Receptors for matrix molecules are likely involved in the mechanical signaling. In the first part of this study we identified integrins with affinity for the cartilage-specific collagen type II. We report that the collagen-binding integrins alpha 1 beta 1 and alpha 2 beta 1 isolated from bovine chondrocytes or human chondrosarcoma cells bound collagen type II as judged from affinity chromatography. The integrins alpha 3 beta 1 or alpha 9 beta 1 did not bind collagen type II-Sepharose. In the second part of the study we investigated the effect of mechanical stress on expression of matrix molecules and integrin subunits. Chondrocytes and chondrosarcoma cells, cultured on uncoated flexible silicone membranes in the presence of serum, were exposed to mechanical stress by the Flexercell system. Dynamic stimulation of chondrocytes for 3 h increased the mRNA expression of collagen type II and aggrecan as judged by Northern blotting, while the beta 1-integrin subunit was not changed. When chondrosarcoma cells were exposed to mechanical stimulation under the same conditions, mRNA expression of alpha 5 was found to increase while beta 1, alpha 2, and alpha v did not increase to significant levels. In another study the effect of mechanical stress on integrins was investigated when the cells were cultured on collagen type II-coated flex-dishes. Three hours of dynamic stress increased the mRNA expression of alpha 2-integrin subunit while the level of mRNA for integrin subunits beta 1, alpha 1, alpha 5, and alpha v showed no or small changes, indicating that matrix components may modulate the expression of integrins during mechanical stress.
机械应力是软骨细胞功能的重要调节因子,但软骨细胞感知机械信号的机制尚不清楚。基质分子受体可能参与机械信号传导。在本研究的第一部分,我们鉴定了对软骨特异性II型胶原具有亲和力的整合素。我们报告,从牛软骨细胞或人软骨肉瘤细胞中分离出的胶原结合整合素α1β1和α2β1,通过亲和层析判断,它们能结合II型胶原。整合素α3β1或α9β1不结合II型胶原琼脂糖。在研究的第二部分,我们研究了机械应力对基质分子和整合素亚基表达的影响。在血清存在下,培养在未包被的柔性硅膜上的软骨细胞和软骨肉瘤细胞,通过Flexercell系统暴露于机械应力。通过Northern印迹法判断,对软骨细胞进行3小时的动态刺激可增加II型胶原和聚集蛋白聚糖的mRNA表达,而β1整合素亚基未发生变化。当软骨肉瘤细胞在相同条件下受到机械刺激时,发现α5的mRNA表达增加,而β1、α2和αv未增加到显著水平。在另一项研究中,当细胞培养在II型胶原包被的柔性培养皿上时,研究了机械应力对整合素的影响。3小时的动态应力增加了α2整合素亚基的mRNA表达,但整合素亚基β1、α1、α5和αv的mRNA水平没有变化或仅有微小变化,这表明在机械应力期间,基质成分可能调节整合素的表达。