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

Authors:
Eunmee Hong
Eunmee Hong
Lawrence Ellison Center for Tissue Regeneration and Repair
Davis | United States
Jasper Yik
Jasper Yik
Lawrence J. Ellison Musculoskeletal Research Center
Sacramento | United States
Derek F Amanatullah
Derek F Amanatullah
Stanford University
Prof. Dominik R Haudenschild, Ph.D.
Prof. Dominik R Haudenschild, Ph.D.
University of California Davis Medical Center
Professor
Arthritis Research
Sacramento, CA | United States

Cartilage 2013 Apr;4(2):177-86

Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis Medical Center, Sacramento, CA, USA.

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.

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Source
http://dx.doi.org/10.1177/1947603512472697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297105PMC

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April 2013
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