Identification of a 3Kbp mechanoresponsive promoter region in the human cartilage oligomeric matrix protein gene.

Authors:
Derek F Amanatullah
Derek F Amanatullah
Stanford University
Jeffrey Lu
Jeffrey Lu
University of Texas at El Paso
United States
Jacqueline Hecht
Jacqueline Hecht
University of Texas Medical School at Houston
Houston | United States
Jasper Yik
Jasper Yik
Lawrence J. Ellison Musculoskeletal Research Center
Sacramento | United States
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

Tissue Eng Part A 2012 Sep 10;18(17-18):1882-9. Epub 2012 Aug 10.

Department of Orthopaedic Surgery, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.

Expression of chondrocyte-specific genes is regulated by mechanical force. However, despite the progress in identifying the signal transduction cascades that activate expression of mechanoresponsive genes, little is known about the transcription factors that activate transcription of mechanoresponsive genes. The DNA elements that confer mechanoresponsiveness within a cartilage gene promoter have yet to be identified. We have established an experimental system to identify the DNA elements and transcription factors that mediate the mechanoresponse of a promoter to nominal compressive stress in primary human chondrocytes and stem cells in a three-dimensional culture system. Our results demonstrate that the proximal 3 Kb of the human cartilage oligomeric matrix protein promoter is sufficient to mediate a mechanoresponse in human articular chondrocytes and stem cells, and that the magnitude of mechanoresponse correlates to the regulation of the endogenous gene at the RNA and protein level. This information is critical to understanding how mechanical force regulates the transcriptional activation of cartilage genes in three-dimensional culture.

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Source
http://dx.doi.org/10.1089/ten.TEA.2011.0497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432897PMC

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September 2012
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