TGF-β Type II Receptor/MCP-5 Axis: At the Crossroad between Joint and Growth Plate Development

Lara Longobardi, Tieshi Li, Timothy J. Myers, Lynda O'Rear, Huseyin Ozkan, Ying Li, Clara Contaldo, Anna Spagnoli

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 (Tgfbr2Prx1KO), 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 Tgfbr2Prx1KO 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.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalDevelopmental cell
Volume23
Issue number1
DOIs
StatePublished - Jul 17 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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