Premium
Fetal Growth Plate
Author(s) -
PROVOT SYLVAIN,
SCHIPANI ERNESTINA
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.076
Subject(s) - microbiology and biotechnology , endochondral ossification , chondrocyte , chondrogenesis , mesenchymal stem cell , hypoxia inducible factors , vascular endothelial growth factor , biology , growth factor , transcription factor , cell growth , chemistry , cartilage , cancer research , anatomy , vegf receptors , biochemistry , receptor , gene , genetics
: Fetal growth plate chondrocyte is a unique mesenchymal tissue, as it is avascular and hypoxic. Yet, chondrocytes not only survive in this environment, but also undergo all cellular processes (proliferation, growth arrest, differentiation, etc.) required for normal endochondral bone development. A crucial mediator of the adaptive response of cells to hypoxia is a transcription factor named hypoxia‐inducible factor 1α (Hif‐1α). One target of Hif‐1α transcriptional activation is the angiogenic factor vascular endothelial growth factor (VEGF), whereas Hif‐1α accumulation is controlled by the von Hippel–Lindau (VHL) tumor suppressor, an E3‐ubiquitin ligase that induces its degradation by the proteasome. We, and others, demonstrated that each component of this pathway is a critical regulator of endochondral bone development. In particular, we previously established that Hif‐1α is a survival factor for hypoxic chondrocytes, and that it also negatively regulates cell proliferation. Interestingly, we also showed that hypoxia increases extracellular matrix accumulation in a Hif‐1α‐dependent fashion. This suggested that Hif‐1α could be critically important not only for cell survival and proliferation but also for cell differentiation. We recently demonstrated that Hif‐1α is indeed a differentiation factor since it is required in mesenchymal cells both for early chondrogenesis, and for joint development.