RRC ID 62265
著者 Rutkowski TP, Kohn A, Sharma D, Ren Y, Mirando AJ, Hilton MJ.
タイトル HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development.
ジャーナル J Cell Sci
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.
巻・号 129(11)
ページ 2145-55
公開日 2016-6-1
DOI 10.1242/jcs.181271
PII jcs.181271
PMID 27160681
PMC PMC4920244
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / metabolism* Bone Development / genetics Cartilage / embryology* Cartilage / metabolism* Cell Differentiation Cell Proliferation Chondrocytes / metabolism* Chondrocytes / pathology* Chondrogenesis* / genetics Gene Expression Regulation, Developmental Hypertrophy Mesenchymal Stem Cells / metabolism Mice Repressor Proteins / metabolism* SOX9 Transcription Factor / metabolism Transcription Factor HES-1 / genetics Transcription Factor HES-1 / metabolism* Transcription, Genetic
IF 4.573
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)