Deng C, Wynshaw-Boris A, Zhou F, Kuo A, Leder P
Department of Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Cell. 1996 Mar 22;84(6):911-21. doi: 10.1016/s0092-8674(00)81069-7.
Endochondral ossification is a major mode of bone that occurs as chondrocytes undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. We have identified a role for fibroblast growth factor receptor 3 (FGFR-3) in this process by disrupting the murine Fgfr-3 gene to produce severe and progressive bone dysplasia with enhanced and prolonged endochondral bone growth. This growth is accompanied by expansion of proliferating and hypertrophic chondrocytes within the cartilaginous growth plate. Thus, FGFR-3 appears to regulate endochondral ossification by an essentially negative mechanism, limiting rather than promoting osteogenesis. In light of these mouse results, certain human disorders, such as achondroplasia, can be interpreted as gain-of-function mutations that activate the fundamentally negative growth control exerted by the FGFR-3 kinase.
软骨内成骨是骨骼形成的主要方式，在此过程中软骨细胞经历增殖、肥大、细胞死亡和成骨细胞替代。我们通过破坏小鼠Fgfr - 3基因，确定了成纤维细胞生长因子受体3（FGFR - 3）在此过程中的作用，结果产生了严重且进行性的骨发育异常，伴有软骨内骨生长增强和延长。这种生长伴随着软骨生长板内增殖和肥大软骨细胞的扩张。因此，FGFR - 3似乎通过一种基本的负性机制调节软骨内成骨，限制而非促进骨生成。根据这些小鼠实验结果，某些人类疾病，如软骨发育不全，可被解释为功能获得性突变，激活了FGFR - 3激酶施加的基本负性生长控制。
