c-Maf Transcription Factor Regulates ADAMTS-12 Expression in Human Chondrogenic Cells

Eunmee Hong, Jasper Yik, Derek F. Amanatullah, Paul E. Di Cesare, Dominik R Haudenschild

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Objective: ADAMTS (a disintegrin and metalloproteinase with thrombospondin type-1 motif) zinc metalloproteinases are important during the synthesis and breakdown of cartilage extracellular matrix. ADAMTS-12 is up-regulated during in vitro chondrogenesis and embryonic limb development; however, the regulation of ADAMTS-12 expression in cartilage remains unknown. The transcription factor c-Maf is a member of Maf family of basic ZIP (bZIP) transcription factors. Expression of c-Maf is highest in hypertrophic chondrocytes during embryonic development and postnatal growth. We hypothesize that c-Maf and ADAMTS-12 are co-expressed during chondrocyte differentiation and that c-Maf regulates ADAMTS-12 expression during chondrogenesis. Design: Promoter analysis and species alignments identified potential c-Maf binding sites in the ADAMTS-12 promoter. c-Maf and ADAMTS-12 co-expression was monitored during chondrogenesis of stem cell pellet cultures. Luciferase expression driven by ADAMTS-12 promoter segments was measured in the presence and absence of c-Maf, and synthetic oligonucleotides were used to confirm specific binding of c-Maf to ADAMTS-12 promoter sequences. Results: In vitro chondrogenesis from human mesenchymal stem cells revealed co-expression of ADAMTS-12 and c-Maf during differentiation. Truncation and point mutations of the ADAMTS-12 promoter evaluated in reporter assays localized the response to the proximal 315 bp of the ADAMTS-12 promoter, which contained a predicted c-Maf recognition element (MARE) at position -61. Electorphoretic mobility shift assay confirmed that c-Maf directly interacted with the MARE at position -61. Conclusions: These data suggest that c-Maf is involved in chondrocyte differentiation and hypertrophy, at least in part, through the regulation of ADAMTS-12 expression at a newly identified MARE in its proximal promoter.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalCartilage
Volume4
Issue number2
DOIs
StatePublished - Apr 2013

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Keywords

  • ADAMTS-12
  • c-Maf transcription factor
  • chondrocytes
  • differentiation
  • hypertrophy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Biomedical Engineering
  • Physical Therapy, Sports Therapy and Rehabilitation

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