Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage
Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage
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DOI：
10.1210/en.2002-220746
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发表时间：
2003-06-01
期刊：
影响因子：
4.8
通讯作者：
Kato, Y
中科院分区：
文献类型：
--
作者：
Makihira, S;Yan, WQ;Kato, Y
研究了甲状腺激素对软骨各区域蛋白聚糖降解的影响。在接受丙硫氧嘧啶治疗的甲状腺功能减退大鼠中，软骨内骨化过程中骨骺软骨中的蛋白多糖降解被显着抑制。然而，注射 T-4 逆转了丙基硫氧嘧啶对蛋白多糖降解的影响。在猪生长板外植体中，T-3 还诱导蛋白多糖分解。 T-3 增加了聚集蛋白聚糖单体和核心蛋白从外植体到培养基中的释放。因此，T-3处理后组织中残留的聚集蛋白聚糖单体水平降低，并且单体失去透明质酸结合能力，表明切割位点位于球间结构域。从暴露于T-3的外植体中释放的聚集蛋白聚糖片段在Glu(373)-Ala(374)处发生切割。主要聚集蛋白聚糖酶切割位点。 T-3 对蛋白聚糖降解的刺激在静息软骨外植体中不如在生长板外植体中显着，并且在关节软骨外植体中几乎检测不到。使用兔生长板软骨细胞培养物，我们探索了可能参与 T-3 诱导的聚集蛋白聚糖降解的蛋白酶，发现 T-3 增强了聚集蛋白聚糖酶-2/ADAM-TS5（一种解整合素和具有 I 型血小板反应蛋白结构域的金属蛋白酶结构域）mRNA 的表达，而我们无法检测到溶基质素、明胶酶或胶原酶活性或任何聚集蛋白聚糖酶-1/ADAM-TS4 的任何增强。 mRNA 表达。我们还发现，软骨内骨化过程中，聚集蛋白聚糖酶 2 mRNA 水平在肥大阶段增加，但聚集蛋白聚糖酶 1 没有增加。这些发现表明聚集蛋白聚糖酶-2/ADAM-TS5 参与软骨内骨化过程中聚集蛋白聚糖的分解，并且甲状腺激素部分通过增强聚集蛋白聚糖酶-2/ADAM-TS5 来刺激聚集蛋白聚糖分解。
Effects of thyroid hormone on proteoglycan degradation in various regions of cartilage were investigated. In propylthiouracil-treated rats with hypothyroidism, proteoglycan degradation in epiphyseal cartilage during endochondral ossification was markedly suppressed. However, injections of T-4 reversed this effect of propylthiouracil on proteoglycan degradation. In pig growth plate explants, T-3 also induced breakdown of proteoglycan. T-3 increased the release of aggrecan monomer and core protein from the explants into the medium. Accordingly, the level of aggrecan monomer remaining in the tissue decreased after T-3 treatment, and the monomer lost hyaluronic acid-binding capacity, suggesting that the cleavage site is in the interglobular domain The aggrecan fragment released from the T-3-exposed explants underwent cleavage at Glu(373)-Ala(374). the major aggrecanase-cleavage site. The stimulation of proteoglycan degradation by T-3 was less prominent in resting cartilage explants than in growth plate explants and was barely detectable in articular cartilage explants. Using rabbit growth plate chondrocyte cultures, we explored proteases that may be involved in T-3-induced aggrecan degradation and found that T-3 enhanced the expression of aggrecanase-2/ADAM-TS5 (a disintegrin and a metalloproteinase domain with thrombospondin type I domains) mRNA, whereas we could not detect any enhancement of stromelysin, gelatinase, or collagenase activities or any aggrecanase-1/ADAM-TS4 mRNA expression. We also found that the aggrecanse-2 mRNA level, but not aggrecanase-1, increased at the hypertrophic stage during endochondral ossification. These findings suggest that aggrecanse-2/ADAM-TS5 is involved in aggrecan breakdown during endochondral ossification, and that thyroid hormone stimulates the aggrecan breakdown partly via the enhancement of aggrecanase-2/ADAM-TS5.