Pereira R C, Jorgetti V, Canalis E
Departments of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford 06105, Connecticut, USA.
Am J Physiol. 1999 Sep;277(3):E496-504. doi: 10.1152/ajpendo.1999.277.3.E496.
Triiodothyronine (T3) increases bone resorption, but its effects on matrix metalloprotease (MMP) expression in bone are unknown. We tested the effects of T3 on collagenase-3 and gelatinase A and B expression in MC3T3 osteoblastic cells. T3 at 1 nM to 1 microM for 24-72 h increased collagenase-3 and gelatinase B mRNA levels, but it did not increase gelatinase A transcripts. In addition, T3 increased immunoreactive collagenase and gelatinase activity. Cycloheximide prevented the stimulatory effect of T3 on collagenase-3 but not on gelatinase B transcripts. Indomethacin did not prevent the effect of T3 on either MMP. T3 did not alter the decay of collagenase-3 or gelatinase B mRNA in transcriptionally arrested MC3T3 cells, and it increased the rate of collagenase-3 and gelatinase B gene transcription. Although T3 enhanced the expression of the tissue inhibitor of metalloproteinase-1 in MC3T3 cells, it increased collagen degradation in cultured intact rat calvariae. In conclusion, T3 increases collagenase-3 and gelatinase B synthesis in osteoblasts by transcriptional mechanisms. This effect may contribute to the actions of T3 on bone matrix remodeling.
三碘甲状腺原氨酸（T3）可增加骨吸收，但其对骨中基质金属蛋白酶（MMP）表达的影响尚不清楚。我们测试了T3对MC3T3成骨细胞中胶原酶-3以及明胶酶A和B表达的影响。1 nM至1 microM的T3作用24至72小时可增加胶原酶-3和明胶酶B的mRNA水平，但不会增加明胶酶A的转录本。此外，T3可增加免疫反应性胶原酶和明胶酶的活性。放线菌酮可阻止T3对胶原酶-3的刺激作用，但不能阻止其对明胶酶B转录本的刺激作用。吲哚美辛不能阻止T3对任何一种MMP的作用。T3不会改变转录停滞的MC3T3细胞中胶原酶-3或明胶酶B mRNA的衰减，并且会增加胶原酶-3和明胶酶B基因的转录速率。尽管T3可增强MC3T3细胞中金属蛋白酶组织抑制剂-1的表达，但它会增加培养的完整大鼠颅骨中的胶原降解。总之，T3通过转录机制增加成骨细胞中胶原酶-3和明胶酶B的合成。这种作用可能有助于T3对骨基质重塑的作用。
