First Author | Zhang Y | Year | 2008 |
Journal | Cell Death Differ | Volume | 15 |
Issue | 11 | Pages | 1760-71 |
PubMed ID | 18636074 | Mgi Jnum | J:154355 |
Mgi Id | MGI:4367681 | Doi | 10.1038/cdd.2008.112 |
Citation | Zhang Y, et al. (2008) Cbfa1-dependent expression of an interferon-inducible p204 protein is required for chondrocyte differentiation. Cell Death Differ 15(11):1760-71 |
abstractText | We reported earlier that an interferon-inducible p204 protein serves as a cofactor of Cbfa1 and promotes osteogenesis. Here we establish that p204 demonstrates prominent expression in growth plate chondrocytes. It is differentially expressed in the course of bone morphogenetic protein-2-triggered chondrocyte differentiation of pluripotent C3H10T1/2 cells. This expression is probably due to the activation of p204 gene by Cbfa1 and repression by Sox5 transcription factor. Cbfa1 and Sox5 bind to the 5'-flanking regulatory region of p204 gene at their consensus binding elements. Overexpression of p204 accelerates chondrocyte hypertrophy, as revealed by enhanced expression of type X Collagen and matrix metalloproteinase-13; however, knockdown of p204 via an siRNA approach abolishes hypertrophic chondrocyte differentiation. p204 acts as a cofactor of Cbfa1 in chondrocyte hypertrophy: (1) overexpression of p204 augments, whereas suppression of p204 decreases, the Cbfa1-dependent transactivation of a Collagen X-specific reporter gene; (2) p204 enhances Cbfa1-mediated chondrocyte hypertrophy; and (3) p204 associates with Cbfa1 in chondrocyte differentiation. In addition, altered expression of p204 in chondrocyte hypertrophy was accompanied by altered levels of Indian hedgehog (IHH) and parathyroid hormone/parathyroid hormone-related peptide receptor-1 (PTHR1). Collectively, p204 is a novel regulator of chondrocyte differentiation by (1) acting as a coactivator of Cbfa1 and (2) affecting IHH/PTPrP signaling. |