Thyroxine stimulates transglutaminase activity in articular chondrocytes.
Thyroxine stimulates transglutaminase activity in articular chondrocytes.
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DOI：
10.1016/s1063-4584(03)00074-8
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发表时间：
2003-06
影响因子：
7
通讯作者：
A. Rosenthal;D. Heinkel;C. Gohr
中科院分区：
文献类型：
--
作者：
A. Rosenthal;D. Heinkel;C. Gohr
ObjectivesThyroid hormones induce features of the hypertrophic phenotype in mature articular chondrocytes as well as in growth plate chondrocytes. Hypertrophic chondrocytes are responsible for extracellular matrix mineralization, with formation of bone mineral in growth plate cartilage and pathologic calcium crystals in aging articular cartilage. Elevated activity levels of the two transglutaminase (Tgase) enzymes (type II Tgase and Factor XIIIA (FXIIIA)) have recently been described as additional features of hypertrophic growth plate chondrocytes. Because Tgases may participate in pathologic mineralization in aging cartilage, we explored the effects of thyroid hormones on Tgase activity in articular chondrocytes.MethodsAdult porcine articular chondrocytes were incubated with or without 250–750nM l-thyroxine (T4) or 10–100nM 3,3′,5-tri-iodothyronine (T3). Tgase activity was measured with a standard radiometric assay. The effects of thyroid hormones on protein and mRNA levels of type II Tgase and FXIIIA were determined. As Tgase activity can be stimulated by proteases, endoproteinase levels were also measured. The mechanisms of these effects were explored.ResultsT4 (750nM) or T3 (100nM) stimulated Tgase activity by twofold in articular chondrocytes at 4h and increased the percentage of Tgase activity in the extracellular matrix. Chondrocytes rapidly converted T4 to T3, but the time course suggests similar mechanisms for T4 and T3. T4-induced Tgase activity was suppressed with cycloheximide and protein kinase C inhibitors. The effects of T4 on type II Tgase and FXIIIA levels were modest, but T4 strongly induced endoproteinase activity in chondrocytes.ConclusionsWe report in this study that thyroid hormones increase Tgase activity in articular chondrocytes via a non-genomic mechanism, which may involve increased endoproteinase secretion.
