The nuclear factor I (NFI) gene family encodes site-specific transcription factors essential for the development of a number of organ systems. Our previous studies indicate that NFI-C is required for tooth root development and bone formation, but the exact function of NFI-C in cartilage development remains unknown. In this study, Nfic-/- mice revealed decreased growth-plate lengths compared with WT. In particular, the width of the proliferating and hypertrophic zone in the growth plate was dramatically reduced in Nfic-/- mice compared with WT. However, NFI-C disruption has no influence on prenatal cartilage development. In addition, cell proliferation rates of Nfic-/- chondrocytes were decreased approximately 40% at 3 days and 70% at 5 days compared with WT, respectively. PCNA-positive cells were significantly diminished in the proliferating zone of Nfic-/- mice compared with WT. In contrast, chondrocyte apoptosis was increased in the hypertrophic zone of Nfic-/- mice compared with WT. Nfic-/- chondrocytes exhibited increased p21 expression but decreased cyclin D1 expression, strongly suggesting cell growth arrest due to the lack of Nfic activity. Further, Nfic-/- chondrocytes exhibited increased caspase-3 activation. These results indicate that NFI-C disruption results in decreased femur length caused by reduction in the width of the growth plate, decreased chondrocyte proliferation, and increased chondrocyte apoptosis.
Disclosure: The authors declared no competing interests. This work was supported by National Research Foundation of Korea Grants NRF-2013R1A2A2A01010911.