HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development

Timothy P. Rutkowski, Anat Kohn, Deepika Sharma, Yinshi Ren, Anthony J. Mirando, Matthew J. Hilton

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders.

Original languageEnglish (US)
Pages (from-to)2145-2155
Number of pages11
JournalJournal of cell science
Volume129
Issue number11
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Chondrocyte hypertrophy
  • Chondrogenesis
  • HES1
  • HES5
  • SOX9

ASJC Scopus subject areas

  • Cell Biology

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