Mechanosensitive promoter region in the human HB-GAM gene.
Mechanical loading is essential for maintaining bone mass in the adult skeleton. However, the underlying process of the transfer of the physical stimulus into a biochemical response, which is termed mechanotransduction is poorly understood. Mechanotransduction results in the modulation of gene expression through specific transcription factor binding sites in the promoter region of mechanosensitive genes. In the present study, we demonstrate that the expression of HB-GAM, which is known to have stimulating effects on osteogenic differentiation, is rapidly induced by mechanical loading in hMSC-TERT4 cells. Analysis of the human HB-GAM gene upstream regulatory region with luciferase reporter gene assays revealed that the upregulation of HB-GAM expression occurred at the transcriptional level and was mainly dependent on the HB-GAM promoter region most upstream containing three potential AP-1 binding motifs.
Liedert
Astrid
A
Institute of Orthopedic Research and Biomechanics, University of Ulm, Germany. astrid.liedert@uni-ulm.de
Kassem
Moustapha
M
Claes
Lutz
L
Ignatius
Anita
A
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D018808:Transcription Factor AP-1 / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D018808:Transcription Factor AP-1; C066845:pleiotrophin; D008156:Luciferases