Zhang Y, Cao L, Kiani C, Yang B L, Hu W, Yang B B
Sunnybrook & Women's College Health Sciences Centre and Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada.
J Cell Biochem. 1999 Jun 15;73(4):445-57.
We have previously demonstrated that versican stimulated NIH3T3 fibroblast proliferation. Since versican is expressed in cartilage, we investigated whether versican plays a role in chondrocyte proliferation. We developed a technique to stably express a recombinant versican mini-gene in chicken chondrocytes, and its effect on chondrocyte proliferation was analyzed by the increase in cell number. The effect of cell adhesion on cell proliferation was tested. Finally, the versican mini-gene was truncated to assess the role of EGF-like motifs in cell proliferation. Expression of the recombinant versican mini-gene stimulated chondrocyte proliferation. Antisense oligonucleotides complementary to versican inhibited chondrocyte proliferation. The G1 domain of versican stimulated chondrocyte proliferation by destabilizing chondrocyte adhesion. Furthermore, deletion of the two EGF-like motifs from the G3 domain also reduced the function of versican in stimulating cell proliferation. Versican enhances chondrocyte proliferation through a mechanism involving its G1 and G3 domains. This finding may have implications for our understanding of the pathogenesis of various joint diseases.
我们之前已经证明，多功能蛋白聚糖能刺激NIH3T3成纤维细胞增殖。由于多功能蛋白聚糖在软骨中表达，我们研究了多功能蛋白聚糖在软骨细胞增殖中是否发挥作用。我们开发了一种在鸡软骨细胞中稳定表达重组多功能蛋白聚糖小基因的技术，并通过细胞数量的增加来分析其对软骨细胞增殖的影响。测试了细胞黏附对细胞增殖的影响。最后，对多功能蛋白聚糖小基因进行截短，以评估表皮生长因子样基序在细胞增殖中的作用。重组多功能蛋白聚糖小基因的表达刺激了软骨细胞增殖。与多功能蛋白聚糖互补的反义寡核苷酸抑制了软骨细胞增殖。多功能蛋白聚糖的G1结构域通过破坏软骨细胞黏附来刺激软骨细胞增殖。此外，从G3结构域删除两个表皮生长因子样基序也降低了多功能蛋白聚糖在刺激细胞增殖方面的功能。多功能蛋白聚糖通过涉及其G1和G3结构域的机制增强软骨细胞增殖。这一发现可能对我们理解各种关节疾病的发病机制具有启示意义。
