Inhibition of chondrocyte terminal differentiation and matrix calcification by soluble factors released by articular chondrocytes
Inhibition of chondrocyte terminal differentiation and matrix calcification by soluble factors released by articular chondrocytes
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DOI：
10.1007/s002239900698
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发表时间：
1999-10-01
影响因子：
4.2
通讯作者：
Fuchihata, H
中科院分区：
文献类型：
--
作者：
Jikko, A;Kato, Y;Fuchihata, H
软骨细胞在正常关节软骨中不经历终末分化，而生长板软骨细胞在终末合成ALTH并诱导基质钙化。骨关节炎关节软骨细胞表达终末分化表型，提示正常关节软骨细胞终末分化受到抑制。在本研究中，我们使用II型胶原包被的培养皿或Millipore过滤器上的新型培养模型研究了关节软骨终末分化的潜在抑制机制，在胶原包被的培养皿上的生长板软骨细胞培养物中，从第7天到第8天，ALcase活性增加，但在关节软骨细胞培养物中没有。当在生长板软骨细胞培养物中混合相同数量的关节软骨细胞时，胶原包被的培养皿上的生长板软骨细胞的ALTH表达被完全抑制。当关节软骨细胞或生长板软骨细胞保持在16 mm培养皿中的Millipore Tillers上时，它们开始合成ALctin。在Millipore过滤器上的软骨细胞的ALTH表达被保持在相同培养皿中的底部胶原包被的基质上的关节软骨细胞的存在抑制。这些结果表明，通过Millipore过滤器扩散到培养基中的因子参与了终末分化的抑制。由于来自关节软骨细胞培养物的条件培养基不影响AL β的表达，因此认为从关节软骨细胞持续释放的可溶性因子负责终末分化的抑制。
Chondrocytes do not undergo terminal differentiation in normal articular cartilage, whereas growth plate chondrocytes synthesize ALPase and induce matrix calcification terminally. Articular chondrocytes in osteoarthritic joints have been reported to express the terminal differentiation phenotypes, suggesting that terminal differentiation of articular chondrocytes is inhibited in normal joints, In the present study, we investigated the underlying inhibitory mechanism of the terminal differentiation in articular cartilage using a culture on type II collagen-coated dishes or a novel culture model on Millipore filters, ALPase activity increased from day 7 to day 8 in growth plate chondrocyte cultures on the collagen-coated dishes, but not in articular chondrocyte cultures. The ALPase expression of growth plate chondrocytes on the collagen-coated dish was completely inhibited when the same number of articular chondrocytes was mixed in the growth plate chondrocyte cultures. When articular chondrocytes or growth plate chondrocytes were maintained on Millipore Tillers held in 16-mm dishes, they started to synthesize ALPase. The ALPase expression of the chondrocytes on Millipore filters was inhibited by the presence of articular chondrocytes maintained on the bottom collagen-coated substratum in the same dishes. These results indicate that factors that diffused into the medium through the Millipore filters are involved in the inhibition of terminal differentiation. Since the conditioned medium from articular chondrocyte cultures did not affect the ALPase expression, it is considered that the soluble factors, which are continuously released from articular chondrocytes, are responsible for the inhibition of terminal differentiation.