Mediation of chondrogenic and osteogenic differentiation by an interferon-inducible p202 protein.
p202, an interferon-inducible protein that belongs to an interferon-inducible p200 family, was highly induced in the course of osteogenesis of pluripotent C2C12 cells and the chondrogenesis of C3H10T1/2 cells. Differential expression of p202 is probably due, at least in part, to the transactivation of the p202 gene by Smad transcription factors. Overexpressing p202 inhibited, whereas lowering p202 via a siRNA approach enhanced, chondrocyte differentiation. In contrast, overexpression of p202 enhanced, whereas knockdown of p202 inhibited, osteoblast differentiation. Molecular mechanism studies revealed that p202 and parathyroid hormone-related peptide (PTHrP) formed a positive feedback loop, since (1) overexpressing p202 markedly enhanced whereas knocking down p202 suppressed the expression of PTHrP; and (2) p202 expression was increased in growth plate chondrocytes of PTHrP receptor transgenic mouse embryos; however, its expression was reduced in PTHrP knockout mouse embryos. Taken together, our findings demonstrate that p202 protein is a novel, important mediator of chondrogenic and osteogenic differentiation.
Kong
L
L
Department of Orthopaedic Surgery, New York University School of Medicine, New York, NY 10003, USA.
Liu
C J
CJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology*; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006132:Growth Plate / Q000166:cytology / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D051785:Smad Proteins / Q000502:physiology
C092537:Ifi202b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D044162:Parathyroid Hormone-Related Protein; D034741:RNA, Small Interfering; D051785:Smad Proteins