Sanjay Saw, Alison Aiken, Hui Fang, Trevor D McKee, Sarah Bregant, Otto Sanchez, Yan Chen, Ashley Weiss, Brendan C Dickson, Bertrand Czarny, Ankit Sinha, Amanda Fosang, Vincent Dive, Paul D Waterhouse, Thomas Kislinger, Rama Khokha
Regulated growth plate activity is essential for postnatal bone development and body stature, yet the systems regulating epiphyseal fusion are poorly understood. Here, we show that the tissue inhibitors of metalloprotease (TIMP) gene family is essential for normal bone growth after birth. Whole-body quadruple-knockout mice lacking all four TIMPs have growth plate closure in long bones, precipitating limb shortening, epiphyseal distortion, and widespread chondrodysplasia. We identify TIMP/FGF-2/IHH as a novel nexus underlying bone lengthening where TIMPs negatively regulate the release of FGF-2 from chondrocytes to allow IHH expression...
September 2, 2019: Journal of Cell Biology