TGF-β type II receptor/MCP-5 axis: at the crossroad between joint and growth plate development

Dev Cell. 2012 Jul 17;23(1):71-81. doi: 10.1016/j.devcel.2012.05.004.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / cytology
  • Cartilage, Articular / embryology
  • Chondrocytes / physiology
  • Female
  • Gene Expression Regulation, Developmental / physiology
  • Growth Plate / cytology
  • Growth Plate / embryology*
  • Joints / cytology
  • Joints / embryology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocyte Chemoattractant Proteins / genetics
  • Monocyte Chemoattractant Proteins / metabolism*
  • Pregnancy
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction / physiology


  • Ccl12 protein, mouse
  • Monocyte Chemoattractant Proteins
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II