Dual regulation of stromelysin-3 by fibroblast growth factor-2 in murine osteoblasts.

The Journal of Biological Chemistry
A M Delany, E Canalis

Abstract

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.

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Citations

Apr 5, 2000·The Journal of Clinical Investigation·A M DelanyE Canalis
Feb 26, 2014·Journal of Translational Medicine·Giuseppe RoscilliLuigi Aurisicchio
Aug 25, 2005·The Journal of Investigative Dermatology·Yumiko Ishimatsu-TsujiJiro Kishimoto
Oct 12, 2010·Molecular Oncology·George S KaragiannisEleftherios P Diamandis
Oct 12, 2005·Developmental Biology·Bernard Thisse, Christine Thisse

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