Delany A M, Canalis E
Departments of Research and Medicine, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
J Biol Chem. 1998 Jun 26;273(26):16595-600. doi: 10.1074/jbc.273.26.16595.
Osteoblasts express stromelysin-3, a matrix metalloproteinase associated with normal remodeling processes and with stromal fibroblasts surrounding many invasive carcinomas. Fibroblast growth factors (FGFs) play an important role in skeletal development, fracture repair, and osteoblast function. The osteoblastic cell line MC3T3 was used to study the regulation of stromelysin-3 by FGF-2. Acutely, FGF-2 decreased stromelysin-3 mRNA levels, whereas prolonged treatment caused an induction of stromelysin-3 mRNA. RNA stability studies and nuclear run-off assays indicated that acute treatment with FGF-2 decreased stromelysin-3 mRNA stability but did not alter gene transcription. However, the induction of stromelysin-3 after prolonged treatment with FGF-2 resulted from increased gene transcription, with no effect on RNA stability. The stimulatory effect was protein synthesis-dependent, whereas the inhibitory effect was not. This study demonstrates dual regulation of stromelysin-3 by FGF-2: acute destabilization of stromelysin-3 mRNA, followed by induction of gene transcription. This complex regulation may be important in the function of stromelysin-3 in bone and in remodeling processes, such as wound and fracture repair.
成骨细胞表达基质溶解素-3，这是一种与正常重塑过程以及许多浸润性癌周围的基质成纤维细胞相关的基质金属蛋白酶。成纤维细胞生长因子（FGFs）在骨骼发育、骨折修复和成骨细胞功能中发挥重要作用。成骨细胞系MC3T3被用于研究FGF-2对基质溶解素-3的调控。急性情况下，FGF-2降低基质溶解素-3 mRNA水平，而长期处理则导致基质溶解素-3 mRNA的诱导。RNA稳定性研究和细胞核转录分析表明，FGF-2急性处理降低了基质溶解素-3 mRNA的稳定性，但未改变基因转录。然而，FGF-2长期处理后基质溶解素-3的诱导是由于基因转录增加，对RNA稳定性无影响。刺激作用依赖于蛋白质合成，而抑制作用则不然。本研究证明了FGF-2对基质溶解素-3的双重调控：基质溶解素-3 mRNA的急性去稳定化，随后是基因转录的诱导。这种复杂的调控可能在基质溶解素-3在骨中的功能以及在诸如伤口和骨折修复等重塑过程中很重要。
