| First Author | MacLean HE | Year | 2003 |
| Journal | Dev Biol | Volume | 262 |
| Issue | 1 | Pages | 51-63 |
| PubMed ID | 14512017 | Mgi Jnum | J:85738 |
| Mgi Id | MGI:2676505 | Doi | 10.1016/s0012-1606(03)00324-5 |
| Citation | MacLean HE, et al. (2003) Absence of transcription factor c-maf causes abnormal terminal differentiation of hypertrophic chondrocytes during endochondral bone development. Dev Biol 262(1):51-63 |
| abstractText | In this study, we report that the transcription factor c-Maf is required for normal chondrocyte differentiation during endochondral bone development. c-maf is expressed in hypertrophic chondrocytes during fetal development (E14.5-E18.5), with maximal expression in the tibia occurring at E15.5 and E16.5, in terminally differentiated chondrocytes. In c-maf-null mice, fetal bone length is decreased approximately 10%, and hypertrophic chondrocyte differentiation is perturbed. There is an initial decrease in the number of mature hypertrophic chondrocytes at E15.5 in c-maf-null tibiae, with decreased expression domains of collagen X and osteopontin, markers of hypertrophic and terminal hypertrophic chondrocytes, respectively. By E16.5, there is an expanded domain of late hypertrophic, osteopontin-positive chondrocytes in the c-maf-/-. This accumulation of hypertrophic chondrocytes persists and is still observed at 4 weeks of age. These data suggest that c-Maf facilitates the initial chondrocyte terminal differentiation and influences the disappearance of hypertrophic chondrocytes. BrdU and TUNEL analyses show normal proliferation rate and apoptosis in the c-maf-null. There is a specific decrease in MMP-13 expression at E15.5 in the c-maf-null. MMP-13 is known to be regulated by AP-1 and may also be a target of c-Maf. Thus, cartilage is a novel system in which c-Maf acts during development, where c-Maf is required for normal chondrocyte differentiation. |
