Delany A M, Canalis E
Department of Research, Saint Francis Hospital and Medical Center, Connecticut, Hartford 06105, USA.
Am J Physiol. 1998 Mar;274(3):C734-40. doi: 10.1152/ajpcell.1998.274.3.C734.
Osteonectin (secreted protein acidic and rich in cysteine, 40-kDa basement membrane) is a glycoprotein abundantly expressed in bone and in other tissues undergoing active remodeling. Fibroblast growth factors (FGFs) are important in skeletal development and fracture repair, events associated with extracellular matrix remodeling. We used the murine osteoblastic cell line MC3T3 to determine whether basic FGF (bFGF) regulates osteonectin expression in bone. Northern blot analysis showed that bFGF decreased osteonectin transcripts in a dose- and time-dependent manner. This regulation was independent of the mitogenic effect of bFGF but was dependent on new protein synthesis. Immunoprecipitation of [35S]methionine-cysteine osteoblast-conditioned medium and cell layer proteins showed that bFGF decreased osteonectin synthesis. Nuclear runoff assays failed to reveal regulation of osteonectin gene transcription by bFGF. However, bFGF dramatically decreased the stability of osteonectin mRNA in transcriptionally arrested osteoblasts. This destabilization of osteonectin mRNA may be one means by which bFGF regulates extracellular matrix remodeling.
骨连接蛋白（分泌性富含半胱氨酸的酸性蛋白，40 kDa 基底膜蛋白）是一种糖蛋白，在骨骼及其他正在进行活跃重塑的组织中大量表达。成纤维细胞生长因子（FGFs）在骨骼发育和骨折修复中发挥重要作用，这些过程与细胞外基质重塑相关。我们使用小鼠成骨细胞系 MC3T3 来确定碱性成纤维细胞生长因子（bFGF）是否调节骨中骨连接蛋白的表达。Northern 印迹分析表明，bFGF 以剂量和时间依赖性方式降低骨连接蛋白转录本水平。这种调节独立于 bFGF 的促有丝分裂作用，但依赖于新的蛋白质合成。对 [35S]甲硫氨酸 - 半胱氨酸标记的成骨细胞条件培养基和细胞层蛋白进行免疫沉淀显示 bFGF 降低了骨连接蛋白的合成。核转录分析未能揭示 bFGF 对骨连接蛋白基因转录的调节作用。然而，bFGF 显著降低了转录停滞的成骨细胞中骨连接蛋白 mRNA 的稳定性。骨连接蛋白 mRNA 的这种去稳定化可能是 bFGF 调节细胞外基质重塑的一种方式。
