Handley Christopher J, Winter Gavin M, Ilic Mirna Z, Ross Jacqueline M, Anthony Poole C, Clem Robinson H
School of Human Biosciences, La Trobe University, Melbourne, Vic 3086, Australia.
Matrix Biol. 2002 Nov;21(7):579-92. doi: 10.1016/s0945-053x(02)00078-1.
This paper describes temporal changes in the metabolism and distribution of newly synthesized aggrecan and the organization of the extracellular matrix when explant cultures of articular cartilage maintained in the presence of fetal calf serum were exposed to retinoic acid for varying periods of time. Explant cultures of articular cartilage were incubated with radiolabeled sulfate prior to exposure to retinoic acid. The radiolabeled and chemical aggrecan present in the tissue and appearing in the culture medium was studied kinetically. Changes in the localization of radiolabeled aggrecan within the extracellular matrix were monitored by autoradiography in relation to type VI collagen distribution in the extracellular matrix. In control cultures where tissue levels of aggrecan remain constant the newly synthesized aggrecan remained closely associated with the territorial matrix surrounding the chondrocytes. Exposure of cultures to retinoic acid for the duration of the experiment, resulted in the extensive loss of aggrecan from the tissue and the redistribution of the remaining radiolabeled aggrecan from the chondron and territorial matrix into the inter-territorial matrix. These changes preceded alterations in the organization of type VI collagen in the extracellular matrix that involved the remodeling of the chondron and the appearance of type VI collagen in the inter-territorial matrix; there was also evidence of chondrocyte proliferation and clustering. In cartilage explant cultures exposed to retinoic acid for 24 h there was no loss of aggrecan from the matrix but there was an extensive redistribution of the radiolabeled aggrecan into the inter-territorial matrix. This work shows that maintenance of the structure and organization of the extracellular matrix that comprises the chondron and pericellular microenvironment of chondrocytes in articular cartilage is important for the regulation of the distribution of newly synthesized aggrecan monomers within the tissue.
本文描述了在含有胎牛血清的条件下维持的关节软骨外植体培养物在不同时间段暴露于视黄酸时，新合成的聚集蛋白聚糖的代谢和分布的时间变化以及细胞外基质的组织情况。在暴露于视黄酸之前，将关节软骨外植体培养物与放射性标记的硫酸盐一起孵育。对组织中以及培养基中出现的放射性标记的和化学性的聚集蛋白聚糖进行了动力学研究。通过放射自显影监测放射性标记的聚集蛋白聚糖在细胞外基质中的定位变化，并与细胞外基质中VI型胶原的分布相关联。在聚集蛋白聚糖组织水平保持恒定的对照培养物中，新合成的聚集蛋白聚糖仍与软骨细胞周围的区域基质紧密相关。在实验期间将培养物暴露于视黄酸，导致组织中聚集蛋白聚糖大量丢失，并且剩余的放射性标记的聚集蛋白聚糖从软骨粒和区域基质重新分布到区域间基质中。这些变化先于细胞外基质中VI型胶原组织的改变，后者涉及软骨粒的重塑以及区域间基质中VI型胶原的出现；也有软骨细胞增殖和聚集的证据。在暴露于视黄酸24小时的软骨外植体培养物中，基质中没有聚集蛋白聚糖的丢失，但放射性标记的聚集蛋白聚糖大量重新分布到区域间基质中。这项工作表明，维持构成关节软骨中软骨粒和软骨细胞周细胞微环境的细胞外基质的结构和组织，对于调节新合成的聚集蛋白聚糖单体在组织内的分布很重要。
