| First Author | Longobardi L | Year | 2012 |
| Journal | Dev Cell | Volume | 23 |
| Issue | 1 | Pages | 71-81 |
| PubMed ID | 22814601 | Mgi Jnum | J:187608 |
| Mgi Id | MGI:5437546 | Doi | 10.1016/j.devcel.2012.05.004 |
| Citation | Longobardi L, et al. (2012) TGF-beta type II receptor/MCP-5 axis: at the crossroad between joint and growth plate development. Dev Cell 23(1):71-81 |
| abstractText | 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-beta-type-II-receptor (TbetaRII) 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 TbetaRII/MCP-5 axis as an essential crossroad for joint development and endochondral growth. |
