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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rutkowski, TP; Kohn, A; Sharma, D; Ren, Y; Mirando, AJ; Hilton, MJ

Published Date

  • June 2016

Published In

Volume / Issue

  • 129 / 11

Start / End Page

  • 2145 - 2155

PubMed ID

  • 27160681

Pubmed Central ID

  • 27160681

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

International Standard Serial Number (ISSN)

  • 0021-9533

Digital Object Identifier (DOI)

  • 10.1242/jcs.181271

Language

  • eng