成纤维细胞生长因子（FGF）、印度刺猬因子（Ihh）/甲状旁腺激素样激素（Pthlh）和骨形态发生蛋白（BMP）信号通路的相互作用整合了软骨细胞的增殖和肥大分化。

Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation.

作者信息

Minina Eleonora, Kreschel Conny, Naski Michael C, Ornitz David M, Vortkamp Andrea

机构信息

Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany.

出版信息

Dev Cell. 2002 Sep;3(3):439-49. doi: 10.1016/s1534-5807(02)00261-7.

DOI:10.1016/s1534-5807(02)00261-7

PMID:12361605

Abstract

Mutations in fibroblast growth factor (FGF) receptor 3 lead to the human dwarfism syndrome achondroplasia. Using a limb culture system, we have analyzed the role of FGF signaling and its interaction with the Ihh/Pthlh and BMP pathways in regulating chondrocyte differentiation. In contrast to previous suggestions, we demonstrate that FGF signaling accelerates both the onset and the pace of hypertrophic differentiation. We furthermore found that FGF and BMP signaling act in an antagonistic relationship regulating chondrocyte proliferation, Ihh expression, and the process of hypertrophic differentiation. Importantly, BMP signaling rescues the reduced domains of proliferating and hypertrophic chondrocytes in a mouse model for achondroplasia. We propose a model in which the balance of BMP and FGF signaling adjusts the pace of the differentiation process to the proliferation rate.

摘要

成纤维细胞生长因子（FGF）受体3的突变会导致人类侏儒症综合征软骨发育不全。利用肢体培养系统，我们分析了FGF信号传导的作用及其在调节软骨细胞分化过程中与Ihh/Pthlh和BMP信号通路的相互作用。与之前的观点相反，我们证明FGF信号传导加速了肥大分化的起始和进程。我们还发现FGF和BMP信号传导在调节软骨细胞增殖、Ihh表达以及肥大分化过程中呈拮抗关系。重要的是，BMP信号传导挽救了软骨发育不全小鼠模型中增殖和肥大软骨细胞减少的区域。我们提出了一个模型，其中BMP和FGF信号传导的平衡将分化过程的速度调整为增殖速率。