Vincent Tonia, Hermansson Monika, Bolton Mark, Wait Robin, Saklatvala Jeremy
The Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College School of Science, Technology, and Medicine, 1 Aspenlea Road, London W6 8LH, UK.
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8259-64. doi: 10.1073/pnas.122033199. Epub 2002 May 28.
The extracellularly regulated kinase (ERK), one of the three types of mitogen-activated kinases, was rapidly activated after cutting porcine articular cartilage either when maintained as explants or in situ. Cutting released a soluble ERK-activating factor from the cartilage, which was purified and identified by MS as basic fibroblast growth factor (bFGF). Experiments with neutralizing Abs to bFGF and an FGFR1 tyrosine kinase inhibitor showed that this growth factor was the major ERK-activating factor released after injury. Treating cartilage with the heparin-degrading enzyme heparitinase also caused release of bFGF, suggesting the presence of an extracellular store that is sequestered in the matrix and released upon damage. Basic FGF induced the synthesis of a number of chondrocyte proteins including matrix metalloproteinases 1 and 3, tissue inhibitor of metalloproteinases-1, and glycoprotein 38, which were identified by MS. The strong induction of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 suggests that bFGF could have a role in remodeling damaged tissue.
细胞外调节激酶（ERK）是三种丝裂原活化激酶之一，在切割猪关节软骨后，无论是作为外植体维持还是在原位，ERK都会迅速被激活。切割从软骨中释放出一种可溶性ERK激活因子，经质谱纯化和鉴定为碱性成纤维细胞生长因子（bFGF）。用抗bFGF中和抗体和FGFR1酪氨酸激酶抑制剂进行的实验表明，这种生长因子是损伤后释放的主要ERK激活因子。用肝素降解酶类肝素酶处理软骨也会导致bFGF的释放，这表明存在一种细胞外储存库，它被隔离在基质中并在损伤时释放。碱性成纤维细胞生长因子诱导了许多软骨细胞蛋白的合成，包括基质金属蛋白酶1和3、金属蛋白酶组织抑制剂-1和糖蛋白38，这些蛋白经质谱鉴定。基质金属蛋白酶和金属蛋白酶组织抑制剂-1的强烈诱导表明bFGF可能在重塑受损组织中起作用。
