title: Identification of a 3Kbp mechanoresponsive promoter region in the human cartilage oligomeric matrix protein gene.
abstract: 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.
authors: Department of Orthopaedic Surgery, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.
authors: Derek F
authors: DF
authors: Amanatullah
authors: Jeffrey
authors: J
authors: Lu
authors: Jacqueline
authors: J
authors: Hecht
authors: Karen
authors: K
authors: Posey
authors: Jasper
authors: J
authors: Yik
authors: Paul E
authors: PE
authors: Di Cesare
authors: Dominik R
authors: DR
authors: Haudenschild
mesh_terms: D000464:Alginates / Q000737:chemistry; D020029:Base Pairing / Q000235:genetics*; D015153:Blotting, Western; D064236:Cartilage Oligomeric Matrix Protein; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D019245:Compressive Strength / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D064235:Matrilin Proteins; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000464:Alginates; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D006603:Hexuronic Acids; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D020723:Glucuronic Acid; D008156:Luciferases