| Literature DB >> 22814601 |
Lara Longobardi1, Tieshi Li, Timothy J Myers, Lynda O'Rear, Huseyin Ozkan, Ying Li, Clara Contaldo, Anna Spagnoli.
Abstract
Despite its clinical significance, the mechanisms of joint morphogenesis are elusive. By combining laser-capture microdissection for RNA sampling with microarrays, we show that the setting in which joint-forming interzone cells develop is distinct from adjacent growth plate chondrocytes and is characterized by downregulation of chemokines, such as monocyte-chemoattractant protein-5 (MCP-5). Using in vivo, ex vivo, and in vitro approaches, we show that low levels of interzone-MCP-5 are essential for joint formation and contribute to proper growth plate organization. Mice lacking the TGF-β-type-II-receptor (TβRII) in their limbs (Tgfbr2(Prx1KO)), which lack joint development and fail chondrocyte hypertrophy, show upregulation of interzone-MCP-5. In vivo and ex vivo blockade of the sole MCP-5 receptor, CCR2, led to the rescue of joint formation and growth plate maturation in Tgfbr2(Prx1KO) but an acceleration of growth plate mineralization in control mice. Our study characterized the TβRII/MCP-5 axis as an essential crossroad for joint development and endochondral growth.Entities:
Mesh：
Substances：
Year: 2012 PMID： 22814601 PMCID： PMC3401383 DOI： 10.1016/j.devcel.2012.05.004
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270