Cbfa1-dependent expression of an interferon-inducible p204 protein is required for chondrocyte differentiation.
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.
Zhang
Y
Y
Department of Orthopaedic Surgery, New York University Medical Center, New York, NY 10003, USA.
Kong
L
L
Carlson
C S
CS
Liu
C-J
CJ
D000818:Animals; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis / Q000187:drug effects; D024121:Collagen Type X / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D006132:Growth Plate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006984:Hypertrophy; D007150:Immunohistochemistry; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D055755:SOXD Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
D055396:Bone Morphogenetic Protein 2; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; C489664:Ifi16 protein, mouse; D009687:Nuclear Proteins; D044162:Parathyroid Hormone-Related Protein; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D055755:SOXD Transcription Factors; C089186:Sox5 protein, mouse; C514061:ihh protein, mouse