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

Rachel A. Kahler, Sorcha M.C. Yingst, Luke H. Hoeppner, Eric D. Jensen, David Krawczak, Julia T. Oxford, Jennifer J. Westendorf

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Alpha 1 (XI) collagen (Col11a1) is essential for normal skeletal development. Mutations in Col11a1 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 Col11a1 transcription. We previously identified Col11a1 as a differentially expressed gene in Lef1-suppressed MC3T3 preosteoblasts. Here we report that Lef1 activates the Col11a1 promoter. This activation is dependent upon the DNA binding domain of Lef1, but does not require the β-catenin interaction domain, suggesting that it is not responsive to Wnt signals. Targeted suppression of Col11a1 with an antisense morpholino accelerated osteoblastic differentiation and mineralization in C2C12 cells, similar to what was observed in Lef1-suppressed MC3T3 cells. Moreover incubation with a purified Col11a1 N-terminal fragment, V1B, prevented alkaline phosphatase expression in MC3T3 and C2C12 cells. These results suggest that Lef1 is an activator of the Col11a1 promoter and that Col11a1 suppresses terminal osteoblast differentiation.

Original languageEnglish (US)
Pages (from-to)330-338
Number of pages9
JournalMatrix Biology
Volume27
Issue number4
DOIs
StatePublished - May 2008

Bibliographical note

Funding Information:
This work was supported by NIH grants AR050074 and AR048147 to JJW, T32-AR050938, AR47985, AR48672, RR16454, Idaho SBOE Musculoskeletal Research Center, Lori and Duane Stueckle Professorship, and funding from the M. J. Murdock Foundation to JTO.

Keywords

  • Beta-catenin
  • Collagen 11a1
  • Lef1
  • Osteoblasts
  • V1b
  • VO
  • Wnt

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