Collagen 11a1 is indirectly activated by lymphocyte enhancer-binding factor 1 (Lef1) and negatively regulates osteoblast maturation

Alpha I (XI) collagen (Col IIaI) is essential for normal skeletal development. Mutations in Col IIaI cause Marshall and Stickler syndromes, both of which are characterized by craniofacial abnormalities, nearsightedness and hearing deficiencies. Despite its link to human diseases, few studies have described factors that control Col IIaI transcription. We previously identified Col IIaI as a differentially expressed gene in Leftsuppressed MC3T3 preosteoblasts. Here we report that Left activates the Col IIaI promoter. This activation is dependent upon the DNA binding domain of Left, but does not require the beta-catenin interaction domain, suggesting that it is not responsive to Writ signals. Targeted suppression of Col IIaI with an antisense morpholino accelerated osteoblastic differentiation and mineralization in C2C12 cells, similar to what was observed in Left-suppressed MC3T3 cells. Moreover incubation with a purified expression in MC3T3 and C2C12 cells. These results suggest that Left terminal osteoblast differentiation. (c) 2008 Elsevier B.V./International Society of Matrix Biology. All rights Col IIaI N-terminal fragment, VIB, prevented alkaline phosphatase is an activator of the Col IIaI promoter and that Col IIaI suppresses reserved.